- Open Access
Effect of mineral excipients on processing traditional Chinese medicines: an insight into the components, pharmacodynamics and mechanism
Chinese Medicine volume 16, Article number: 143 (2021)
Traditional Chinese medicines are an important class of natural products mainly derives from animals, plants and minerals, most of which need to be improved and processed before clinical use due to their own hard texture, impurities or toxicity. As an important part of solid excipients, mineral excipients that contain some metal elements play indispensable and unique roles in the pretreatment process of traditional Chinese medicine. However, deficiency of holistic understanding of the effect of mineral excipients hinders their application and development. This article reviews several mineral excipients including alumen, talci pulvis, soil, soda lime, halloysitum rubrum and cinnabaris systemically. Their processing significance on traditional Chinese medicines were revealed from components, pharmacodynamics and mechanism aspects. Furthermore, prospect and problems including processing technologies, quality standards of mineral excipients and processing mechanism were put forward. This review supply comprehensive information for better and scientific usage of mineral excipients in processing traditional Chinese medicines.
Traditional Chinese medicines (TCM) are an important class of natural products mainly derives from animals, plants and minerals, most of which need to be improved and processed before clinical use due to their own hard texture, impurities or toxicity, and the pretreatment process is called Chinese medicine processing. In the process of processing, the active ingredients such as alkaloids, glycosides, volatile oils, tannins, organic acids, proteins, amino acids, sugars and inorganic compounds will be affected. Generally, the processing methods of TCM are mainly divided into cleaning, cutting, heating, and adding excipients. Cleaning is used to remove the impurities and non-medicinal parts. Cutting contributes to the decoction of effective components through changing the shape of medicinal materials. Heating is applied to changing the texture and efficacy, correcting the bias, improving the decoction of effective ingredients as well as reducing toxicity and side effects through the procedures of frying, calcining, steaming, boiling, etc. . Adding excipients could not only change the nature, flavor, action and meridian tropism of crude drugs, but also enhance the efficacy and reduce or diminish the toxicity and side effects. Among which, the application of excipients that possesses a long history has reflected the flexibility of clinical medication. And the role in processing medicinal materials is also variable accompanied by the difference between varieties, properties and functions of excipients.
Overall, processing excipients could be divided into liquid excipients and solid excipients. Yellow rice wine, vinegar, salt-water and refined honey are the commonly used liquid ones. Yellow rice wine could promote the upward direction, enhance the effect of blood-activating and stasis-resolving medicinal in invigorating blood circulation, moderate the cold and cool of some herbs with cold-nature .Vinegar could reinforce the effect of liver-soothing, dissipating blood stasis and relieving pain of TCM synergistically. Besides, several TCM processed with salt-water could conduct the drug to the kidney meridian and strengthen the efficacy on lower-jiao diseases. Refined honey could change drugs become sweet and sluggish, enhance the effects of benefiting Qi, moistening lung, relieving a cough and stopping pain and dysentery. In addition, ginger juice, licorice juice, black bean juice, bile, lanolin and sesame oil that are used for specific herbs also belongs to the categories of liquid excipients. As for solid excipients, rice could generally reduce the odor and toxicity of animal drugs and increase the role of some tonic drugs in improving the interior and benefiting Qi. Bran could absorb excessive volatile oil and reduce irritation of herbs. Sand helps the medicine to be friability due to homogeneous heating and reduces the toxicity as well. Except for the above commonly used ones, some mineral excipients that not only acts as medicinal materials but also enhance the therapeutic effect and reduce the toxicity were also applied in the process of TCM.
In the Chinese Pharmacopoeia (ChP, 2020 edition), 4 kinds of TCM that processed with mineral excipients has been included. Pinelliae Rhizoma Praeparatum Cum Alumine (Qingbanxia), Pinelliae Rhizoma praeparatum cum Zingibere et Alumine (Jiangbanxia), and Rhizoma Pinelliae Praeparatum (Fabanxia) that derive from the raw Pinellia ternate (Thunb.) Breit. were processed with alumen, ginger juice and soda lime as adjuvant materials, respectively. Arisaematis rhizoma preparatum (Zhitiannanxing) that derives from the Arisaema erubescens (Wall.) Schott, Arisaema heterophyllum Bl. or Arisaema amurense Maxim. is processed with alumen. Besides, Typhonii Rhizoma (Baifuzi) and Hirudo (Shuizhi) that were separately processed with alumen and talci pulvis has also been included as one of the main processing methods, although relative standards have not formed. Meanwhile, some provinces have promulgated their own standards. For example, Atractylodis Macrocephalae Rhizome (Baizhu) and Paeoniae Radix Alba (Baishao) that stir-fried with soil have been included in the standard for preparation of Chinese herbal pieces in Beijing (2008 edition). Coicis Semen (Yiyiren) stir-fried with soil has been included in the standard for cut crude drug of TCM in Yunnan Province (2005 edition). Moreover, several processed products including Angelicae Sinensis Radix (Danggui) stir-fried with soil, Ophiopogonis Radix (Maidong) mixed with Cinnabaris had also been included in provincial processing specification, even though there is still no formal standards to follow (Table 1). The aforementioned information suggests the essential role of mineral excipients in the field of TCM processing. However, their research status and processing mechanism has not been systematic summarized, which hinders their application and development.
In this paper, the application of several mineral excipients in the processing of TCM is reviewed by sorting out the existing literature reports (Fig. 1, Table 1). Their processing significance on TCM were revealed from components, pharmacodynamics and mechanism aspects, which provides references for better usage of TCM.
Effect of mineral excipients on the processing of TCM
Alumen is a kind of sulfate mineral alumen stone, which is processed and refined from alunite. It can be used as an external medicine to exert the effects of detoxification, insecticidal, moisturizing and relieving itching as well as oral administration for diseases such as bleeding and diarrhea. Apart from the above physical and biological actions as a TCM, the alumen itself is often used as a processing excipient to reduce toxicity and increase efficacy. Banxia, Baifuzi and Tiannanxing are typical TCM processed with alumen (Fig. 2).
The processing method of Banxia and Tiannanxing with alumen could be traced back to the Song Dynasty. The former has been recorded in many classical medical books in China, such as Taipinghuiminhejijufang(《太平惠民和剂局方》), Shengjizonglu(《聖濟總錄》) and Baoqingbencaozhezhong(《宝庆本草折衷》), while the latter was first documented by Shengjizonglu [3,4,5]. Besides, standards for the processed products of Baifuzi with alumen have been included in the ChP and 26 provincial processing specifications, which is gradually developed on the basis of previous licorice and ginger processing. So far, boiling or steaming Baifuzi with alumen or ginger has become the universal processing means .
Pinelliae Rhizoma, commonly known as 'Ban-xia' in Chinese, is botanically from the dried tuber of Pinellia ternata (Thunb.) Breit., which has been used to remove dampness and dissipate phlegm, reduce adverse reactions, stop vomiting as well as eliminate swelling and scattered nodules. Furthermore, it is also a famous poisonous plant, and its toxicity is attributed to alkaloids and toxic proteins. Lectin is the most important toxic component of Banxia. And it has been confirmed to have obvious toxic damage to many organs, such as liver, digestive tract, kidney and heart. Interestingly, when verifying the toxic effect of Banxia on stomach and digestive tract, some researchers found that 50 mg/mL of Banxia could inhibit gastric nerve activity in rats, while it did not show any inhibitory effect when processed with ginger juice. Moreover, it also exhibits obvious reproductive toxicity, which lead to the termination of pregnancy and fetal deformity or death. Animal experiments showed that intragastric administration of Banxia powder (9 g/kg) and Banxia decoction (30 g/kg) could increase early embryo mortality by 85.7% and 50.0%, respectively [7,8,9]. Similarly, Banxia no longer causes vomiting and hoarseness in experimental animals after the processing with alumen .
As one of the classic herbs processed by alumen, the contents of alkaloids, organic acids, nucleotides, polysaccharides, proteins, amino acids and inorganic elements in Banxia were mainly changed. Ephedrine, a major alkaloid constituent that relieves cough and asthma, its content increases after processing due to nonvolatile and stabilization of ephedrine salt formed by the action of acidic alumen water [10,11,12]. In addition, there are also cases where the content of alkaloid is lower than that of raw one by different processing technology [10, 13]. For example, a significant decrease in the content was observed in other alkaloids including guanosine, uridine and adenosine compared with the crude product, which may be related to the breaking and decomposition of glycosidic bond by dissolving in water and alumen [10, 11, 13,14,15,16]. Moreover, changes of these three alkaloid components could affect the expectorant effect of Banxia. Meanwhile, content of organic acid such as succinic acid in processed Banxia was usually higher than that of raw products . While it was also reported that their content was slightly lower or similar to that of the raw one. The main reason was that the total organic acid was dissolved in water, and the difference would occur owing to the different processing parameters .
Detoxification is also one of the main purposes of Banxia processing, calcium oxalate needle crystal with special crystalline and lectin protein are main toxic components in it. After being processed with alumen, the toxic needle crystal dissolved and corroded, and the agglutinin protein degraded and denatured, so the toxicity is reduced [10, 14, 17,18,19,20,21,22,23]. However, the lectin protein is also an effective component of Banxia with anti-tumor effect . Thus, explore how to moderately processing Banxia with alumen has important implications.
The content of amino acids in processed Banxia was higher than that in the raw one . It was also reported that the quantity and species of amino acids, sugars, fatty acids and phytosterols had no change, while the content was much lower than that of crude drugs . The sugar content decreased significantly because of its dissolution in water. In addition, the strong acid action of aluminum can degrade triacylglycerol into diacylglycerol, monoacylglycerol and glycerol . Some trace elements also changed, the content of zinc, magnesium and iron in inorganic elements increased sharply accompanied by the introduction of nickel at the same time [10, 13]. Some studies still pointed out that the reducing sugar content of Qingbanxia is higher than that of the raw one, conversely, the total sugar content is lower .
Comparative investigation of curative effect and aluminum residue after alum processing is also worthy of attention. The content of succinic acid and alkaloids increased after the preparation of Banxia by alumen, which was beneficial to improve several therapeutic effects, such as antitussive, antiasthmatic, anti-ulcer, etc. . And alumen itself has the effect of dispelling wind phlegm, which helps enhance the therapeutic effect of Banxia. Besides, decrease of some proteins, polysaccharides and nucleotides can also affect the anticancer effect of Banxia, but the irritant toxicity of raw one is significantly reduced after being processed with alumen. It has been reported that there is aluminum residue after alum processing in Banxia. However, some aluminum ions are converted into stable small toxic granular aluminum due to the intense boiling conditions, which reduces the direct toxicity of aluminum in Banxia to human body  (Table 2).
Arisaematis Rhizoma, commonly known as ‘Tian-nan-xing’ in Chinese, is botanically from the dried tuber of Arisaema erubescens (Wall.) Schott, Arisaema heterophyllum Bl. or Arisaema amurense Maxim., which has the effect of dispersing knot and detumescence. While Tiannanxing is usually used to dry dampness and resolve phlegm, dispel wind and stop spasm as well as disperse knot and detumescence. However, its obvious toxicity was recorded in ancient books and reported by modern research. Dong et al. used the metabonomics method to reveal its nephrotoxicity mechanism. After intragastric administration of rat Tiannanxing (0, 0.5 and 1 g/kg body weight) for 30 days, the levels of serum urea nitrogen and creatinine were significantly increased. Significant changes of metabolites in blood and urine were also observed . Similarly, another study revealed neurotoxic effects of Tiannanxing when given ICR mice for 3 days. However, it is worth noting that Tiannanxing that processed with alumen and ginger juice or bile not only reduced the neurotoxic effect but also enhanced the neuropharmacological effect . After processing, the contents of amino acids and alkaloids are lower than that of raw products, which is similar to that of Banxia . The content of inorganic elements zinc and calcium is lower than that of raw product, in return, the iron element obtained higher content, which indicates the introduce or loss of inorganic elements by processing . At the same time, the agglutinin protein is degraded accompanied by the dissolution of toxic calcium oxalate needle crystal due to acid alumen water, and alumen is hydrolyzed into aluminum hydroxide to form gelatin, which reduce its toxicity by adsorption of toxic component owing to the electric charge [21,22,23, 28, 29].
Typhonii Rhizoma, commonly known as ‘Bai-fu-zi’ in Chinese, is botanically from the dried tuber of Typhonium giganteum Engl, which has been used to dispel wind and phlegm, calm convulsion, detoxification and relieve pain. However, its significant toxicity could not be ignored. Wang et al. treated RAW264.7 cells with different doses of Banxia lectin and found that inflammatory cytokines increased in a dose-dependent manner. Moreover, strong toxic effects related to inflammation were produced by long-term stimulation . Compared with the raw materials, the contents of alkaloids, total saponins, nucleosides and other components of Baifuzi were changed after the process. Besides, new organic substances were generated, which promoted and strengthened the therapeutic effect of processed product. Significantly, the process of producing 5-hydroxymethylfurfural (5-HMF) by alumen water and heating could be attributed to the sugar thermal degradation and Maillard reaction of the sugars and amino acids of Baifuzi itself under the action of temperature and PH. Although 5-HMF has some toxic and side effects, it also possesses the effects of anti-oxidation and improving hemorheology, which increases the efficacy of Baifuzi in treating headache and vertigo of phlegm syncope. And 5-HMF was further transferred into bis (5-formylfuryl) ether by dehydration and condensation, which had antiviral, antioxidant and inhibitory effects on Mycobacterium tuberculosis. Meanwhile, the formation of above two organics has close association with the heating time and alumen consumption [31, 32].
The agglutinin protein contained in Baifuzi was degraded and denatured after being processed in alumen water [21, 22]. In addition, the loss of water-soluble free amino acids is relatively larger in the processing, the total amino acid content decreased by about 30% compared with the crude product, and the liposoluble components content increased, which was related to the alum fixation of protein and the promotion of lipid synthesis [32,33,34,35]. Meanwhile, the content of total alkaloids decreased greatly, which may be caused by the formation of soluble salt between acid alumen water and alkaloids [34, 36, 37]. Nucleosides, a class of biomolecules easily dissolved in water, their content was lower than that of raw product [34, 36]. Besides, the content of total flavonoids and saponins decreased slightly, while that of polysaccharides did not decrease significantly . It is the same as Banxia processed with alumen, the aluminum content in Baifuzi processed with alumen is hundreds of times higher than that in raw one, which is due to the large amount of aluminum ions introduced from alumen [32, 34].
Generally, alumen is mainly used for processing plants of the genus Araceae for reducing their toxicity. Apart from the three typical medicinal materials described above, the toxicity of Alocasia Macrorrhiza (Haiyu), the dried tuber of Alocasia macrorrhiza (L.) Schott, is also reduced due to the processing of alumen, while its antipyretic effect is weakened as well . Cordate Pinellia Tuber (Dishuizhu), the dried tuber of araceae plant Pinellia cordata N. E. Br., another kind of Araceae plants, whose number of components with low polarity and chemical composition changed little after being processed by alumen. However, its high polar components decreased significantly due to promotion dissolution of small molecular compound with high polarity by the aluminium potassium sulphate in alumen .
Gardeniae Fructus (Zhizi), originate from the dry ripe fruit of Gardenia jasminoides Ellis, has also been reported to be processed with alumen. According to Tang’s study, the content of active ingredients such as total iridoid glycosides, geniposide, crocin I and crocin II extracted from Zhizi with six edges had been increased significantly after being boiled in alumen water . Correspondingly, their curative effect was enhanced as well. However, there is some evidence that these ingredients will be reduced after being processed with alumen . The divergence could be attributed to the different varieties or processing conditions. And all this has important significance to the improvement of the processing technology for the retention of active ingredients. In the literature and traditional processing methods of Zhizi, alumen water boilling has also been used to kill enzyme and reserve glycosides . Furthermore, alumen could enhance the coloring of natural pigment, while the pigments of Zhizi could be widely used in food and textile industry . Therefore, this method could reduce the environmental disruption to the quality of Zhizi due to the component loss caused by storage time.
Talci pulvis is widely used as a TCM, which possess the effect of diuresis, clearing away heat and detoxification, collecting dampness as well as astringent sores. Likewise, talci pulvis also plays an important role in the processing of TCM from three aspects. First, toxic and side effects of several toxic and irritating herbs including Roudoukou, Strychni Semen (Maqianzi), Aristolochia Manshuriensis (Guanmutong), Shuizhi and Bufonis Venenum (Chansu) could be reduced. Second, a synergistic action could be observed in some medicinal materials when processed with talci pulvis, such as Galli Gigerii Endothelium Corneum (Jineijin), Ejiao, Pheretima (Dilong). Third, some animal medicinal materials including swim bladder, corium elephatis and hedgehog skin were usually processed by talci pulvis in order to change the content of active ingredients and make the texture crisp and convenient for preparation (Fig. 3).
The application of talci pulvis in processing has been gradually developed according to the clinical requirement, although there were no relative records in ancient times. Most notably, the processing method of Hirudo with talci pulvis has been included in the ChP, National Standard for preparation of Chinese Materia Medica and the processing specifications of Guangxi, Henan, Heilongjiang, Jiangxi and other provinces. While that of Ejiao was recorded in the processing specifications of Hunan and Jiangxi Province [43, 44].
Myristicae Semen, commonly known as ‘Rou-dou-kou’ in Chinese, is botanically from the seed kernel of Myristica fragrans Houtt. As a kind of major active component in Roudoukou, volatile oils bring us not only antibacterial, anti-inflammatory, anti-oxidation and other therapeutic effects but also intestinal sliding and toxic irritation. Although the raw material shows a variety of pharmacological activities, overdose can also lead to varying degrees of toxicity. Several literatures have reported that its toxic dose is 5 g, but some researchers have found that the 1–2 mg/kg of Roudoukou is enough to cause neurotoxicity. In addition, its hepatotoxicity, carcinogenicity and cytotoxicity that is closely related to its main active components (myristicin, safrole, engenol, elemicin, etc.) has also been reported . Therefore, proper processing is beneficial for retaining its efficacy and reducing its stimulation. Among the constituents which contained in Roudoukou, monoterpenoids and aromatic compounds rank the first two place. Monoterpenoids were degraded or volatilized due to the high temperature with talci pulvis processing, while the content of aromatic compounds increased. In addition, destroyed hydroxyl structure and conversion into monoterpenes without oxygen atoms may lead to the decrease of efficacy . As for the volatile oils, the content of myristicin, eugenol, isoeugenol, safrol and methyl eugenol was increased after being processed with talci pulvis [46, 47]. Among them, myristicin exhibited resistance against hepatic lipid peroxidation but hallucinogenic, eugenol and isoeugenol possessed antioxidant activity, safrol and methyl eugenol had carcinogenic and genotoxic effects. However, some studies showed that the content of myristicin decreased after processing with talci pulvis and that of safrol changed irregularly, which may be attribute to the variation in processing time and temperature [48, 49]. If the processing time was too short, the content of myristicin has instead increased . The results indicated that the processing conditions showed great effect on its curative effect and toxicity.
Moreover, the property of talci pulvis is not consistent with the antidiarrheal effect of Roudoukou, so the efficacy, toxicity and other factors should be considered before we decide whether to use talci pulvis to process Roudoukou. It has been reported that the content of volatile oils in Roudoukou showed a trend of "first decreased and then rose" along with decreased particle size and increased dosage of talci pulvis . These phenomena may be related to the heat transfer rate, particle size of powder, adsorption and other factors. While the stability of dehydroisoeugenol is less affected by these factors . In addition to the effect on volatile oils, content of some inorganic elements such as Fe, Mn, Zn, Cu, Ca, Mg, Cr, Ni, Co and Po were also increased . Briefly, appropriate processing conditions with talci pulvis could reduce the irritation and increase the content of effective components of Roudoukou, reasonable and unified processing technology that ensures the therapeutic effect need further study.
Some herbs containing toxic components were usually processed with talci pulvis for detoxification. Metal elements are widely regarded as toxic ingredients of Shuizhi, Pb, Cd and Hg contained therein were decreased after processing . Hirudin, a major active ingredient of Shuizhi that affects its thrombolytic effect, its content was also reduced [51,52,53]. Instead, the content of amino acid in processed Shuizhi was obviously higher than that in raw products because proteins were more likely decomposed into small peptide and free amino acid at high temperature [51, 53, 54]. There are other studies showed that hypoxanthine increased significantly after processing [51, 53, 54]. Besides, some trace elements were also affected, the content of Ca and Mg increased, while that of Zn, Mn, Cu and Fe decreased . Meanwhile, some volatile components were lost along with the produce of new ones [51, 55].
It is noteworthy that although the toxicity of Shuizhi is reduced due to the processing of talci pulvis, the efficacy of Shuizhi and some other toxic TCM were also affected accordingly. For example, bufogenin and resibufogenin in Chansu, strychnine and brucine in Maqianzi, which are all active but toxic, could be reduced after processed with talci pulvis [56,57,58,59]. Guanmutong, a controversial medicinal material with severe nephrotoxicity, had been removed from the ChP, because of its toxic component aristolochic acid A, which can be destroyed about 40% by the high temperature processing of talci pulvis . Therefore, the appropriate technology for reducing the toxicity and retaining the efficacy when processing toxic herbs with talci pulvis should be given in the future research.
In addition to reducing toxicity, enhancing the efficacy is also a mechanism of talci pulvis application. For example, a synergistic role could be observed when Jineijin and Pheretima was used for stranguria, heat-clearing and diuretic, respectively [61, 62]. The reason why Jineijin is used for digestion after processed with talci pulvis is probably related to the increase of protease activity, but the amylase activity is lower than that of raw product . It can be inferred that processed Jineijin is more suitable for the indigestion that caused by eating too much food with high protein content. Besides, the content of total and essential amino acids in Ejiao increased apparently after processing with talci pulvis, along with its enhanced hemostatic and blood-enriching effect . The mechanism may be associated with the magnesium silicate contained in talci pulvis, which not only promote the produce of a large amount of colloidal protein and calcium salt but also enhance the present convergent, absorption, promoting blood coagulation and reducing bleeding effect .
When talci pulvis is used as a processing auxiliary material, it acts as an intermediate heat transfer body with strong fluidity and fine powder, which is suitable for processing animal medicinal materials with strong toughness. The smashing rate and protein content of the swim bladder are closely related to the dosage of talci pulvis. Generally, more talci pulvis is associated with fuller swim bladder glue swell, higher grinding efficiency and more preserved protein . After processing, some new volatile components such as 3,4,5-trimethoxytoluene, α-gurulene, 3-methyl biphenyl and caryophyllene oxide were produced by the swim bladder and hawksbill shell along with the loss of volatile components 2-decennal, myristic aldehyde, cedarene and valenciennes . Moreover, the content of amino acids in corium elephatis increased after processing, while that in dog testes and penis and hedgehog skin decreased, which was related to heating time and temperature [66,67,68]. It is also noteworthy that these animal medicinal materials are not commonly used in clinical in view of wildlife conservation, although included in some local standards. In general, we used this method to process animal medicinal materials mainly because we can mask the disagreeable odors and make them crisp for decocting the active ingredients. There are also other examples that processed with talci pulvis. For example, the effect on invigorating spleen and relieving diarrhea of Puerariae Lobatae Radix (Gegen) is strengthened after processing with talci pulvis. The phenomenon is mainly resulted from the increased content of total flavonoids . Moreover, processing these herbs with talci pulvis remain one of the most popular approaches recorded in some provincial processing standards, although have not yet been included in ChP.
In traditional Chinese medicine processing, the soil could be used as medicine to stop bleeding, nausea and diarrhea. Normally, the soil we use is the burnt loess in the stove where farmers burn firewood. We call it “Zao-xin-tu”, also known as “Fu-long-gan”. Many alternatives are virtually used due to its rareness. After being roasted in the soil, many medicinal materials possessed the functions of soothing the stomach, stopping vomiting and diarrhea as well as reducing gastrointestinal irritation. The main reason is that the mineral and inorganic salts of the soil could be decomposed into a variety of basic oxides after being heated and refined at high temperature, which neutralized gastric acid and play a role of heat conduction as well . In general, drugs with spleen-tonifying and antidiarrheal effects need to be stir-fried with soil, such as Danggui, Baizhu, Baishao, Yiyiren, Dioscoreae Rhizoma (Shanyao) and so on (Fig. 4).
Products of Danggui, Baizhu, Baishao, and Yiyiren that stir-fried with soil were recorded in historical document Bencaohaili(《本草害利》), Depeibencao(《得配本草》) , Qianjinyifang (《千金翼方》) , Bencaomengquan(《本草蒙筌》)  and Bencaocongxin(《本草从新》) , respectively. And they were also included in the ChP and some local regulations as shown in Table 1.
Angelicae Sinensis Radix
Angelicae Sinensis Radix, commonly known as ‘Dang-gui’ in Chinese, is botanically from the dried root of umbelliferae plant Angelica sinensis (Oliv.) Diels. It could be used to nourish blood, promote blood circulation, regulate menstruation, relieve pain, moisten intestines and defecation. Volatile oils served as a kind of its major active component. After stir frying, the volatile components of Danggui, such as ligustilide, senkyunolide I, senkyunolide H and senkyunolide A, were destroyed and lost due to high temperature . Yet it's worth noting that part of the efficacy was weakened by the reduction of volatile oils when compared with crude herbs, irritation of medicinal materials was also alleviated. Besides, the content of chlorogenic acid increased due to its improved solubility in organic solvent at high temperature, while that of ferulic acid decreased on account of the thermal instability . As for coniferyl ferulate, whose content was increased because the activity of its degrading enzyme was destroyed with the increase of temperature .
Angelica sinensis polysaccharide, a kind of water-soluble macromolecular component, has the effects of improving blood system, promoting immunity, anti-tumor and anti-radiation. After processing, the content of water-soluble sugar, reducing sugar and polysaccharide in Danggui was lower than that in raw product because of carbonization by high temperature, but the decrease was not significant . In addition, formic acid, acetic acid and 1-ethoxypropane showed a relative upward tendency, while N-butylphthalide and N-butenylphthalide decreased significantly . Some studies showed that the content of volatile oil in Danggui decreased significantly after being processed with soil, which could alleviate the irritant intestines, reduce the toxic and side effects, and improve its spleen-tonifying, antidiarrhea, anti-inflammation and hepatoprotective activity [78, 79].
Atractylodis Macrocephalae Rhizoma
Atractylodis Macrocephalae Rhizoma, commonly known as ‘Bai-zhu’ in Chinese, is botanically from the dried rhizome of compositae plant Atractylodes macrocephala Koidz., which could strengthen spleen, replenish Qi, dry dampness and promote diuresis. Atractylenolides, atractylone, volatile oils and polysaccharides are the major active components of it. After processing with soil, the content of atractylenolide I, II and III increased, while that of atractylone decreased . The main reason is that Baizhu became loose after crushing, atractylone was oxidized into atractylenolide I, III and biatractylolide by contacting with oxygen, and atractylenolide III was further transformed into atractylenolide II during the heating dehydration process [79, 80]. Meanwhile, the decrease of atractylone contributed to reduced stimulation . The content of polysaccharide, the main component of invigorating the spleen and stopping diarrhea, had no significant change, while the content of water-soluble sugar increased significantly. Similarly, other components such as elemene, palmitic acid and linoleic acid increased significantly .
Paeoniae Radix Alba
Paeoniae Radix Alba, commonly known as ‘Bai-shao’ in Chinese, is botanically from the dried root of ranunculaceae plant Paeonia lactiflora Pall..It could be used to nourish blood and regulate menstruation, astringe Yin and stops weating, soften liver and relieve pain as well as stabilize liver yang. Paeoniflorin and albiflorin, two major ingredients of Baishao recorded in ChP, were slightly increased after being fried in soil . There were other studies, though, which reported the content of paeoniflorin was lower than that of raw products [81, 82]. The phenomenon was caused partly by the decomposition of paeoniflorin into albiflorin under the catalysis of high temperature conditions and auxiliary ingredients . Therefore, different processing conditions lead to the different contents of active ingredients. Recently, some scholars compared the antioxidant capacity of raw and processed products of Baishao. The antioxidant capacity of processed one is stronger in view of the increased gallic acid and benzoic acid after soil processing . Likewise, spleen-strengthening and anti-diarrhea effect of Baishao was also enhanced. This is a result for the one side from the assist of the effective components by the trace elements in soil, and for the other side from the its own hemostasis and anti-vomiting characteristics of soil during cooling and anti-diarrhea process .
Process with soil usually changes the active ingredients and enhance the curative effect of some TCM with spleen-strengthening activity. Take Yiyiren as an example, its dissolution of oil components and the content of triglyceride was increased due to the looser texture after the process with soil . Moreover, the relative increased lactones and changed the oil composition was also observed owing to the absorption effect of soil. As for Lablab Semen Album (Baibiandou), the content of protein and free amino acid were increased accompanied by the decrease of total phospholipid and lectin after process . Accordingly, its effect on regulating gastrointestinal hormone level, strengthening spleen and stopping diarrhea was enhanced. There are also some reports of Chenpi that have been processed with soil, whose content of hesperidin was increased . However, content of polysaccharide, allantoin and phospholipid of Shanyao decreased because of the high temperature [80, 85]. Apart from the above cases, trace elements in Atractylodis Rhizoma (Cangzhu) were also changed. The levels of Fe, Cr, Ti, Al and TL increased by 2 ~ 4 times, while that of Cu, Na, Mg, Sr, Ba, Cd and Li decreased by 2–3 times . Besides, the content of aromatic compounds in Roudoukou changed greatly, except for the decreased myristate and increased safrole, a new component α-asarone was produced accordingly . Besides, soil process could make the rubber filament of Eucommiae Cortex (Duzhong) easier to break and improve the peculiar smell of GGEC [87, 88].
Soda lime is a mixture of calcium hydroxide, sodium hydroxide or potassium hydroxide, which could also be used as pharmaceutical excipients that reduces toxic components in the processing of TCM. The medicinal materials processed with soda lime are Guanmutong, Banxia and other araceae plants (Fig. 5). The processing of Banxia with soda lime water can be traced back to the Ming Dynasty, which is recorded for the first time in the Yaoxingcuping(《药性粗评》). In addition, they were also mentioned in Yaoxinghuiyuan(《药性会元》) and Bencaogangmushiyi(《本草纲目拾遗》) . At present, the pharmaceutical standard of soda lime water-processing Banxia has been included in the ChP. The processing method of Tiannanxing with soda lime water can be found in the work Xianshoulishangxuduanmifang(《仙授理伤续断秘方》) of the Tang Dynasty. SS processed with soda lime water is a folk method. When used in Yangjiang area, the toxicity of it can be greatly reduced .
The detoxification mechanism of processing Banxia by soda lime water was similar to that of processing it with alumen. Moreover, the alkaloids and proteins, two kinds of effective and toxic components in Banxia, were also decreased [10, 91]. The change of trace elements is illustrated by the increase of Zn content and production of new element Ni . Miao medicine Arisaema Rhizomatum (Banjielian), which is the dried tuber of araceae plant Arisaema rhizomatum C.E.C. Fischer. When processed by soaking or steaming in soda lime water, the content of total flavonoids in Banjielian decreased significantly, while that was increased when dry soda lime was used .
Dishuizhu has strong irritation to the mucous membrane of eyes, throat, intestines and stomach, so its processed products are used in clinic for its lower toxicity and resistance. After processed with soda lime water, the number and content of the chemical components in Dishuizhu were both affected, and the decreased content of total alkaloids, uridine and adenosine in which is most obviously . The reason for the results may be that toxic components were mainly small molecules of acidic components and could be removed by the neutralization with soda lime water. In alkaline solution, meanwhile, the loss of uridine and adenosine is large .
As we mentioned above, aristolochic acid A is the toxic component of Guanmutong, which was usually processed with talci pulvis. Significantly, its toxicity could also be reduced by boiling or steaming with soda lime water in view of the reaction with strong alkali supported by soda lime water . Soda lime water can also reduce the toxicity of other herbs, such as Paridis Rhizoma (Chonglou), Haiyu, and Maqianzi. However, their detoxification mechanism is still unclear, which needs further study [93, 94]. Promoting the formation of active ingredients is another processing mechanism of soda lime water. Indigotin, an active component of Indigo Naturalis (Qingdai) was formed and enriched by the promotion of soda lime water through providing alkaline environment, CO2 and carrier .
Some literatures also mentioned the enhanced antidiarrheal and anti-inflammatory effect of guava leaf and holly leaf and reduced toxicity of Huechys (Hongniangzi) by processed with soda lime. Besides, soda lime could also prolong the storage life of Dilong by providing strong alkaline and hygroscopic environment .
Halloysitum rubrum is a silicate mineral, which has the effect of astringent intestines, hemostasis, myogenesis and sores, and is often used as a processing excipient for soil frying in the process of TCM processing .
Roudoukou could be processed by halloysitum rubrum for both reducing the side effects of diarrhea caused by absorption of oil and increasing the antidiarrheal effect . Likewise, immunity, anti-oxidation, anti-inflammatory and anti-cancer effects of Baizhu were also enhanced by halloysitum rubrum for the increased effective components atractylenolide III and polysaccharide, especially the atractylenolide III, whose content was about 3–4 times higher than the raw product .
Cinnabaris is a kind of sulfide mineral medicine, which has the effects of clearing the heart, calming the mind, brightening the eyes and deintoxication, but is toxic. Cinnabaris is usually prepared by elutriation to reduce the content of sulfur and calcium, so as to reduce toxicity and improve cleanliness. Although the toxicity of cinnabaris is reduced after processing, it is rarely used as an excipient when processing TCM due to the dosage that need to be controlled. The method of processing Maidong with cinnabaris was recorded in the reading of Bencaobiandu(《本草便读》) in the Qing Dynasty, and the use of cinnabaris mixed Maidong appeared in Wujutongyian(《吴鞠通医案》) and Bencaohaili(《本草害利》) for the first time. There is little discussion on the tracing of ancient books on processing Yuanzhi with cinnabaris, but some documents mention that this processing method has been used since ancient times and is still in use at present [100, 101].
Generally, it could be used to process some TCM with anti-anxiety and psychotherapeutic activity on the premise of paying attention to the usage and dosage. Studies had shown that, after processing, the content of cyclosenegenin in Yuanzhi was 6 times higher than that of the raw product, while that of senegenic acid and senegenin was basically unchanged . Some studies have questioned the method of processing Maidong with cinnabaris , mainly because of its toxicity and decreased total flavonoids after process . Overall, the processing technology of cinnabaris used for preparing TCM should be further standardized in order to ensure the efficacy and reduce the side effects, which realize its full synergy potential.
To sum up, mineral excipients play an irreplaceable role in the processing of TCM. Among them, alumen and soda lime mainly work at reducing the toxicity of the main drug, but the effective components will also be affected, and thus bring weaker curative effect than that of raw products. Talci pulvis are usually used for processing some medicinal materials containing volatile oils, which relieve gastrointestinal irritation under the premise of ensuring the efficacy and degrade the toxic components of some toxic medicinal materials under high temperature. In addition, some animal medicinal materials could also be deodorized and flavored after processing with talci pulvis, which make their texture crispy and convenient for dispensing. Soil possessed anti-emetic, astringent and hemostatic effects for gastric. It is generally used as auxiliary materials to process herbs with spleen-strengthening and antidiarrhoeal effects and the mechanism was related to enhancing the efficacy and alleviating the irritation through changing the content and composition of volatile oils in herbs. Halloysitum rubrum, as an alternative to the soil, exhibited astringent intestines and antidiarrheal activity by reducing the oil content of medicinal materials. Cinnabaris is an auxiliary material that enhances the heart-clearing and sedative effect of herbs and should be used cautiously due to its toxicity. However, due to their own particularity and affect by various factors, investigated in many aspects including processing technologies, quality standards of mineral excipients and processing mechanism need further study and discuss.
Standardization of processing methods
The processing methods including processing temperature, time, acid–base environment and dosage of excipients need to be standardized, so that the effective components of medicinal materials could be fully retained without increase or decrease inconsistently, which greatly ensures the effectiveness of medicinal materials. Besides, the toxic components of many drugs are also active ingredients. How to retain the maximum effectiveness and reduce the harmfulness as much as possible needs to start from the processing technology for unified specification. Standardization of processing technology can better control the quality standard of processed medicinal materials.
Quality control of mineral excipients
Some mineral excipients such as cinnabaris are toxic or harmful to the human body. Hg2+, HgCl, Hg (CH2COOH)2 and other trace elements such as Ba, Sb are the main toxic components of cinnabaris . Their metabolism is slow and easy to cause heavy metal accumulation, resulting in liver and kidney injury. Moreover, aluminum accumulation of alumen will affect the development of bone cells  and could even lead to visual, memory and other neurological disorders like Alzheimer's disease . Thus, their content, purity and dosage are necessary to control when used as excipients, which help to reduce the loss of effective ingredients and residues of harmful substances.
In-depth study on processing mechanism
For now, the variety in the content and composition of active ingredients from many herbs before and after excipients processing is still unclear with inferred results. Significantly, the mechanism research should be combined with pharmacological research in order to explore which are the active ingredients, how to reduce component loss and toxicity as well as better processing technologies.
Study on the processing of medicine food homology plants
Some medicine food homology plants including Shanyao, Yiyiren and Baizhu were usually fried with soil. After processing, their spleen-strengthening and antidiarrhoeal effects on stomach had been increased. When used as food, however, whether their soil fried products with increased efficacy could be used and how to define the quality standards need in-depth discussion.
The processing of TCM has received more and more attention with the development of analytical technology and toxicological research. As an important part of the processing field, the mineral excipients have played an essential and indispensable role in TCMs application. In this review, the significance of mineral excipients including alumen, talci pulvis, soil, soda lime, halloysitum rubrum and cinnabaris on TCMs has been summarized from the insight into the components, pharmacodynamics and mechanism, which not only supply comprehensive information on how to balance the necessity and relative merits and disadvantages of mineral excipients in clinical application, but also provide a reference for exploring better processing excipients and technology so as to reserve the efficacy as well as reduce toxic and side substances to the human body.
Availability of data and materials
Zhao ZH, Liang K, Chan GH, et al. A unique issue in the standardization of chinese materia medica: processing. Planta Med. 2010;76:1975–86. https://doi.org/10.1055/s-0030-1250522.
Wu X, Wang SHP, Lu JR, Jing Y, Li MX, Cao JL, Bian BL. Seeing the unseen of Chinese herbal medicine processing (Paozhi): advances in new perspectives. Chin Med. 2018;13:4. https://doi.org/10.1186/s13020-018-0163-3.
Liu JY. Taiping Huimin Hejiju Fang. Beijing: People’s Publishing House; 1985.
Zhao J. Shengji Zonglu. Beijing: People’s Publishing House; 2004.
Zheng JS. A Great Dictionary of Chinese Culture: Medical and health volumes: Pharmacy volumes:, vol. 5. Chengdu: Prachuap Khiri Khan books; 2007.
Chinese Pharmacopoeia Commission. First Volume of Pharmacopoeia of People's Republic of China. Beijing: China Medical Science Press; 2015.
Ji X, Huang BK, Wang GW. The ethnobotanical, phytochemical and pharmacological profile of the genus Pinellia. Fitoterapia. 2014;93:1–17. https://doi.org/10.1016/j.fitote.2013.12.010.
Huang FY, Gao JM, Gon QH. Research progress on pharmacological effects and toxicity of Pinellia ternate. Nat Prod Res Dev. 2020;10(32):1773–81. https://doi.org/10.16333/j.1001-6880,2020.10.020.
Gong DF, Wang FC, Ji DH, Zhan L. Research Progress in chemical constituents, Pharmacological and Toxicological of Pinelliae Rhizoma. J Yangtze Univ. 2015;18(12):77–9. https://doi.org/10.16772/j.cnki.1673-1409.2015.18.035.
Bai ZL, Ren YZh, Chen YL, Jin F, Zhou L, Du J, Liang H, Wang Y. Research progress of Pinelliae Rhizoma Praeparatum Cum Alumine. Mod Chin Med. 2014;16(5):423–7.
Huang W, Huang YY, Dai YP, Zhang LM, Sun R. Comparative study on the content of toxical substances and acute toxicity of Shandong Pinelliae and its processed products. Chin J Pharmacovig. 2010;07(11):653–5. https://doi.org/10.3969/j.issn.1672-8629.2010.11.005.
Wu H, Tan XH, Cai B, Ye DJ. Effect of ginger-processing on I-ephedrine contents in Rhizoma Pinelliae. Chin J Chin Mater Med. 1996;21(3):157–8.
Jia LD. Research progress on processing of Pinelliae Rhizoma. Mod Chin Med. 2007;9(2):31–3. https://doi.org/10.3969/j.issn.1673-4890.2007.02.011.
Sun LM, Zhang B, Wang YCh, He HK, Chen XG, Wang SJ. Metabolomic analysis of raw Pinelliae Rhizoma and its alum-processed products via UPLC-MS and their cytotoxicity. Biomed Chromatogr. 2019;33(2):e4411. https://doi.org/10.1002/bmc.4411.
Wu H, Wen HM, Guo R, Ye DJ. Effect of ginger processing on contents of guanosine in Pinelliae Rhizoma(BanXia). Chin J Chin Mater Med. 1998;23(11):21–3.
Liang J, Wang HJ, Zhang ZhL. Effect of integrated processing technology on alkaloids of Pinelliae Rhizoma. Lishizhen Med Mater Med Res. 2017;28(2):357–9. https://doi.org/10.3969/j.issn.1008-0805.2017.02.036.
Yuan HJ, Jia XB, Yin WJ, Wang H, Wang HJ, Li W. Effects of processing on toxic components of Pinellia Rhizoma and its detoxification mechanism. Chin J Chin Mater Med. 2016;41(23):4462–8. https://doi.org/10.4268/cjcmm20162327.
Ji XQ, Huang ChQ, Zhang G. Toxic components and processing mechanism of Rhizoma Pinelliae. Lishizhen Med Mater Med Res. 2019;30(7):1717–20. https://doi.org/10.3969/j.issn.1008-0805.2019.07.065.
Wu H, Zhong LY, Li W, Ye DJ. Study on processing mechanism of Pinellia ternate. Chin J Chin Mater Med. 2007;32(14):1402–6. https://doi.org/10.3321/j.issn:1001-5302,2007.14.006.
Zhu FG. The inflammation-causing effects of agglutinin and mechanism of detoxification processing of Pinellia ternate (Thunb.) Breit and Pinellia pedatiecta Schott. J Nanjing Univ Tradit Chin Med; 2012.
W. Wang, Study on the pro-inflammatory mechanism of four lectins in Araceae and its effect by processing, J. Nanjing Univ. Tradit. Chin. Med., (2019).
Yu HL, Wang W, Wu H, et al. Effect of processing on toxic components lectin from four kinds of Araceae toxic medicines. Chin J Chin Mater Med. 2019;44(24):5398–404. https://doi.org/10.19540/j.cnki.cjcmm.20190916.302.
Huang QW, Guo ZX, Ma LK, Zhang WT, Sheng Y, Chen H, Zhao WL. Analysis on processing of toxic TCM in Zhejiang Province of Processing Chinese Crud Drugs 2015 Edition. Chin J Mod Appl Pharm. 2016;33(6):786–9. https://doi.org/10.13748/j.cnki.issn1007-7693.2016.06.027.
Lee JY, Park NH, Lee WW, Kim EH, Jin YH, Seo EK, Hong JK. Comprehensive chemical profiling of Pinellia species tuber and processed Pinellia tuber by gas chromatography-mass spectrometry and liquid chromatography-atmospheric pressure chemical ionization-tandem mass spectrometry. J Chromatogr A. 2016;1471:164–77. https://doi.org/10.1016/j.chroma.2016.10.033.
Ma Sh, Yang XM, Zhao RH. Speciation analysis of aluminum in Rhizoma Pinelliae before and after alum processing. Chin J Spectrosc Lab. 2011;28(6):2983–6. https://doi.org/10.3969/j.issn.1004-8138.2011.06.054.
Huang CF, Yang RS, et al. Evidence for Improved Neuropharmacological Efficacy and Decreased Neurotoxicity in Mice with Traditional Processing of Rhizoma Arisaematis. Am J Chin Med. 2011;5(39):981–98. https://doi.org/10.1142/S0192415X11009354.
Wei YJ, Zhang BL, Yang ZhL, Du H, He ZJ. Effects of processing on contents of amino acid and part of inorganic elements in Arisaema Amurense Maxim. Chin Tradit Pat Med. 2001;23(4):258–60. https://doi.org/10.3969/j.issn.1001-1528.2001.04.009.
Tang LY, Wu HW, Wang ZJ, He Y, Fu MH. Investigation of attenuating toxicity mechanism of processing for Arisaema erubescens (I). Chin J Exp Tradit Med Form. 2012;18(24):28–31. https://doi.org/10.13422/j.cnki.syfjx.2012.24.065.
Yu HL, Pan YZ, Wu H, Ge XY, Zhang Q, Zhang FG, Cai BCh. The alum-processing mechanism attenuating toxicity of Araceae Pinellia ternata and Pinellia pedatisecta. Arch Pharm Res. 2015;38(10):1810–21. https://doi.org/10.1007/s12272-015-0556-0.
Wang W, Wu H, Yu HL, Zhang XD, Cui GJ, Wang KL, et al. Typhonium giganteum Lectin Exerts A Pro-Inflammatory Effect on RAW 2647 via ROS and The NF-κB Signaling Pathway. Toxins. 2017;9(9):275. https://doi.org/10.3390/toxins9090275.
Zhang HW. The study on the newly added chemical constituent from processed Rhizoma Typhonii. J Henan Univ Tradit Chin Med; 2009.
Li YF, Ma YL. Historical evolution and modern research of Typhonii Rhizoma. Acta Chin Med Pharm. 2010;38(4):105–6. https://doi.org/10.3969/j.issn.1002-2392.2010.04.044.
Yao ST, Fu GL, Hong HY. Comparative analysis on chemical constituents between new and old products of Typhonii Rhizom. Chin J Chin Mater Med. 1993;18(04):212–4.
Gao ShY, Xie MH, Tan HX, An N, Li D, Li L. Advances on preparation and pharmacological activities of Typhonium giganteum. Chin Tradit Herbal Drugs. 2019;50(8):1992–7. https://doi.org/10.7501/j.issn.0253-2670.2019.08.033.
Zhang ZhL, Yang ZhX, Feng WSh, Zhang HW, Liu B. Influence of different processing methods on the content of amino acids in Typhonii Rhizoma. J Chin Med Mater. 2008;31(12):1791–3. https://doi.org/10.3321/j.issn:1001-4454.2008.12.007.
Yu Y. Study on quality-efficiency evaluation of Typhonii Rhizoma and its processed material. J Guangdong Pharm. Unniv; 2015.
Li XD, Mao ShJ, Fu MH, Zhang CY, Cheng LP. Effect of processing with excipients on known components of Typhonii Rhizoma. J Chin Med Mater. 1997;020(002):74–7. https://doi.org/10.13863/j.issn1001-4454.1997.02.011.
Zhang JR, Li YH, Wu QH, Long C, Han J. Preliminary study on analgesic and antipyretic actions of decoction of Alocasia Macrorrhiz and its different processed products. N J Trad Chin Med. 1997;29(8):31–3. https://doi.org/10.13457/j.cnki.jncm.1997.08.019.
Jie H, Zhao YL, Fan RH, Su C, Yu ZG. Comparison of the chemical components of Cordate Pinellia Tuber and its processed products. Chin Pharm. 2011;22(3):231–3.
Tang WW, Wang YP, Lei JW, Ji L, Zhang WF, Xie CX, Yang CJ. Quality evaluation of different fruit-shaped Gardenia jasminoides prepared by Alum based on chemical pattern recognition method. J Chin Med Mater. 2020;43(7):1603–8. https://doi.org/10.13863/j.issn1001-4454.2020.07.012.
Liang XK, Wang YH, Lei JW, Xie CX, Tang WW, Du TT. Effect of different initial processing methods on quality of gardenia. Chin J Chin Mater Med. 2018;43(16):3285–90. https://doi.org/10.19540/j.cnki.cjcmm.20180611.004.
Qian J, Lu W. Study on optimization of gardenia yellow pigment dyeing silk fabric. Mod Silk Sci Technol. 2017;32(6):1–3. https://doi.org/10.3969/j.issn.1674-8433.2017.06.001.
Health Department of Hunan Province. Processing specification of traditional Chinese medicine in Hunan Province. Changsha: Hunan Science Press; 2010. p. 500–1.
Food J, Administration D. Processing Standard of Chinese herbal pieces in Jiangxi Province. Shanghai: Shanghai Science Press; 2008. p. 485–6.
Ma K, Nan XM, Zhao J, Wang YP, Li ZQ, Lu DX. Research progress on pharmacological and toxicological effects of Myristica fragrans. Pharm Clinics Chin Mater Med. 2021. https://doi.org/10.13412/j.cnki.zyyl.20210806.001.
Huang X, Yang XW. GC-MS analysis of essential oil from Nutmeg processed by different traditional methods. Chin J Chin Mater Med. 2007;32(16):1669–75. https://doi.org/10.3321/j.issn:1001-5302.2007.16.018.
Li N, Tan YJ, Yang M. Study on processing technology of stir-frying Nutmeg with Talcum powder. Heilongjiang Med J. 2018;42(9):856–9. https://doi.org/10.3969/j.issn.1004-5775,2018.09.004.
Jia TZh, Yuan ChL, Cao KH, Fu BQ. Determination of myristicine and safrole in volatile oil from different processed products of Myristicae Semen by TLC scanning. Chin J Chin Mater Med. 1991;16(5):275–8.
Li TL, Zhou J, Jiang WJ, Li C. Study on the effect of processing on the volatile oil and myristicine content of Myristicae Semen. Chin J Chin Mater Med. 1990;15(8):23–5.
Chen LK, Li ShH. Study on the processing of Myristicae Semen. J Chin Med Mater. 2002;25(3):174–6. https://doi.org/10.3321/j.issn:1001-4454.2002.03.010.
Ma L, Ma L, Wang ShB, Wang X, Yue L. Review on scientific connotation of leech processed under high temperature. Chin J Chin Mater Med. 2015;40(19):3894–8. https://doi.org/10.4268/cjcmm20151935.
Dai ZB. Determination of hirudin in Hirudo and its processed products. Seek Med Ask Med. 2012;10(12):343–4.
Zhang YT. Quality comparison of Hirudo before and after processed by french chalk. Chin J Chin Mater Med. 2008;33(7):766–8. https://doi.org/10.3321/j.issn:1001-5302.2008.07.008.
Zhang YT. Determinationg of hypoxanthine in Hirudo. Chin Tradit Pat Med. 2008;30(8):1175–7. https://doi.org/10.3969/j.issn.1001-1528.2008.08.024.
Sui LQ, Wu ZhL, Chen YP. Effect of processing on volatile components of six animal Chinese medicinal materials based on SPME-GC-MS analysis. J Chin Med Mater. 2019;42(5):1030–7. https://doi.org/10.13863/j.issn1001-4454.2019.05.015.
Xu BJ, Xia HL, Zhao XJ, Li JH. Effect of processing on bufogenin in Bufonis Venenum. Chin J Chin Mater Med. 1998;12(12):722–3.
Zhao LL, Cao Y, Luo GA, Wang YM. Effect of processing on four bufadienolides in Bufonis Venenum. Chin Tradit Pat Med. 2009;31(5):759–60. https://doi.org/10.3969/j.issn.1001-1528.2009.05.030.
Fu L, Sha Y, He DM. Determination of bufogenin in different processed products of Bufonis Venenum. J Chin Med Mater. 1990; 13(2): 25–27. https://doi.org/10.13863/j.issn1001-4454.1990.02.013
Jiang YH, Li J, Gong QF. Determination of strychnine and brucine in the decoction of Semen Strychni and its different processed products. Chin J Inform Tradit Chin Med. 2008;15(4):47–9. https://doi.org/10.3969/j.issn.1005-5304.2008.04.020.
Pan JH, Yan GJ, Song J. The determination of aristolochic acid A in different processed Aristolochia manshuriensis and the test of influence about renal function in rats. J Chin Med Mater. 2010;33(8):1228–33.
Wang BQ, Lu WCh. Discussion on processing technology of Pheretima. Str Pharm J. 2012;24(4):34–6. https://doi.org/10.3969/j.issn.1006-3765.2012.04.013.
Li ChJ, Chu Sh. Jineijin various accessories of the activity of processed products by HPLC and amino acid. Chin Mod Doc. 2009;47(15):74–5. https://doi.org/10.3969/j.issn.1673-9701.2009.15.033.
Yan NN, Xiong SQ, Chen HP, Liu YP, Chen L. Historical evolution and modern research development in processing Asini Corii Colla. J Chin Med Mater. 2018;41(12):2948–52. https://doi.org/10.13863/j.issn1001-4454.2018.12.046.
Meng XM. The operation technology and clinical application of Talci Pulvis in the preparation of Asini Corii Colla. Xinjiang J Tradit Chin Med. 1995;3:42–3.
Li N, Tan YJ, Wang NM, Feng LL, Yang M. Optimization of processing technology of stir-frying Swim Bladders with talcum powder. Chin Pharm. 2017;26(13):5–8. https://doi.org/10.3969/j.issn.1006-4931.2017.13.002.
Zhao B, Liu J, Wang Q, Cao H. Study on talcum powder ironing process of Corium Elephatis and analysis content of amino acid before and after processing. J Chin Med Mater. 2016;39(6):1272–5. https://doi.org/10.13863/j.issn1001-4454.2016.06.017.
Zhao B, Liu J, Wang Q, Cao H, Wen CSh. Study on the optimization of processing technology of dog testes and penis processed with talcum powder and its quality standard. Chin Pharm. 2016;27(19):2681–3. https://doi.org/10.6039/j.issn.1001-0408.2016.19.28.
Zhao B, Wang Q, Liu J, Cao H, Zheng YP. Process optimization of scalding Hedgehog skin with talcum powder and formulation of quality standard. Chin Tradit Pat Med. 2016;38(8):1869–72. https://doi.org/10.3969/j.issn.1001-1528.2016.08.047.
Zhong K, He JY. Determination of total flavonoids indifferent processed products of Puerariae Lobatae Radix. J GuiYang C Tradit Chin Med. 2004;26(4):59–61. https://doi.org/10.3969/j.issn.1002-1108.2004.04.044.
Chen KL, Chen HP, Chen L. Historical evolution and modem research development of soil processing in traditional Chinese medicine. Chin For Med Treat. 2009;28(1):154–6. https://doi.org/10.3969/j.issn.1674-0742.2009.01.131.
Liang F. Herbal Textual Study of Daodi Chinese Materia Medica. Beijing: Beijing University of traditional Chinese Medicine; 2013.
Sun SM. Qian Jin Yi Fang. Beijing: People’s Medical Publishing House; 1982.
Zhang YS. Ben Cao Meng Quan. Beijing: Traditional Chinese Medicine Ancient Books Publishing House; 2008.
Lu Z. Ben Cao Cong Xin. Beijing: China Traditional Chinese Medicine Press; 2013.
Ji P, Hua YL, Xue WX, Wu HY, Guo YS, Wei YM. Extraction and composition analysis of essential oil from raw Radix Angelicae Sinensis and its different processed products. Nat Prod Res Dev. 2012;24(9):1230–4, 1238. https://doi.org/10.3969/j.issn.1001-6880.2012.09.017.
Hua YL, Xue WX, Zhang M, Wei YM, Ji P. Metabonomics study on the hepatoprotective effect of polysaccharides from different preparations of Angelica sinensis. J Ethnopharmacol. 2014;151(3):1090–9. https://doi.org/10.1016/j.jep.2013.12.011.
Zhong LJ, Hua YL, Ji P, Yao WL, Zhang WQ, Li J, Wei YM. Evaluation of the anti-inflammatory effects of volatile oils from processed products of Angelica sinensis radix by GC MS-based metabolomics. J Ethnopharmacol. 2016;191:195–205. https://doi.org/10.1016/j.jep.2016.06.027.
Chen HP. Study on the mechanism of Atractylodes fried by soil to strengthen spleen and relieve diarrhea. J Chengdu Univ Tradit Chin Med; 2011.
Shen JT, Zhang ZhL. The changes of atractylenolide I, III contents in raw Atratylodes and processed Atratylodes. Lishizhen Med Mater Med Res. 2014;25(8):1873–5. https://doi.org/10.3969/j.issn.1008-0805.2014.08.030.
Shen JT. Study on technical specification of processing Chinese material medica---stir-baked with soil. J Henan Univ Chin. Med; 2014.
Liu SX, Li Y, Feng J, Liu Y, Chang CQ. Influence of processing on the content of paeoniflorin and albiflorin in Paeoniae Radix Alba. Drug Eval Res. 2010;33(2):125–8.
You GJ, Li ChH, Mao YY, Ren XL, Liu YN, Wang M. A comparative analysis of raw and processed Radix Paeoniae Alba samples using HPLC, chemometrics, and antioxidant activity. Biomed Chromatogr. 2020;34(9):e4901. https://doi.org/10.1002/bmc.4901.
Fang M. Study on quality control and the effect of spleen and antidiarrheal of Lablab semen album with fried processing. J Shanxi Univ Chin Med; 2017.
Ding Ch, Zheng YP, Chen L. Effect of four processing methods on the contents of hesperidin and rutnaringin in Pericarpium Citri Reticulatae. Chin Pharm. 2020;29(21):9–11. https://doi.org/10.3969/j.issn.1006-4931.2020.21.003.
Du ShL, Li XK, Zhang ZhL. The effects of different processing methods on the content of polysaccharides of Dioscoreae Rhizoma. J Chin Med Mater. 2010;33(12):1858–61. https://doi.org/10.13863/j.issn1001-4454.2010.12.016.
Li KP, Liu RH, Liu HX, Li F, Yan RN. Comparison of trace elements in CangZhu before and after processing. J GuangDong Trace Elem Sci. 1998;5(10):62–3. https://doi.org/10.16755/j.cnki.issn.1006-446x.1998.10.009.
Chen J, Shen F, Gao L. Study on the processing method of Eucommiae Cortex by soil-processed and spraying salt water. Shananxi J Tradit Chin Med. 2001;22(8):493. https://doi.org/10.3969/j.issn.1000-7369.2001.08.038.
Jiang Y, Wu BZh. Study on the soil-processed technology of Galli Gigerii Endothelium Corneum. Str Pharm J. 1997;9(4):133.
Lin DR. Xianshou Lishang Xuduan Mifang. Beijing: People's Medical Publishing House; 1957. P. 8,17,18.
Li G, Li XN, Zhang RK. The Processing of Research and Clinical Applications of Yangjiang Jiuzhi Maqianzi. Guangxi J Tradi Chin Med. 2001;1(24):47–8. https://doi.org/10.3969/j.issn.1003-0719.2001.01.042.
Li ShH, Yu HL, Wu H, Zheng YB, Wang W. Effect of Pinelliae Rhizoma processed with lime and licorice on toxic lectin protein. Chin J Chin Mater Med. 2020;45(11):2546–51. https://doi.org/10.19540/j.cnki.cjcmm.20200328.308.
Nie ChP, Ran HX, Du J. Determination of total flavonoids in different processed varieties of the Miao medicine Arisaema rhizomatum. Chin J Ethnomed Ethnopharm. 2017;26(10):8–11.
Liu LM, Chen Ch, Cui ZhH, Nian SH. Study on processing technology of Colloid Paris Polyphylla with limewater. Guangzhou Chem Ind. 2019;47(3):57–9. https://doi.org/10.3969/j.issn.1001-9677.2019.03.022.
Kang HY. Study advance on limewater in the traditional Chinese medicine processing. Nei Mongol J Tradit Chin Med. 2016;35(9):99. https://doi.org/10.3969/j.issn.1006-0979,2016.09.095.
Nian SH, Liu LM, Bao ShY, Zhang YH. Study advance on limewater in the traditional Chinese medicine processing. Chin Med Herald. 2011;08(36):13–4. https://doi.org/10.3969/j.issn.1673-7210.2011.36.005.
Chen YD. Processing excipient—Halloysitum Rubrum, J. Zhenjiang Coege TCM, 22(2) (1998) 50. Doi: https://doi.org/10.16466/j.issn1005-5509.1998.02.039.
Cai WSh. Discussion on theprocessing method of Myristicae Semen. Str Pharm J. 2003;15(5):85–6. https://doi.org/10.3969/j.issn.1006-3765.2003.05.054.
Chen HP, Liu YP, Liu ChP, Li P. Content comparison of atractylode III and soluble polysaccharide of Atractylodes macrocephala processed with different kinds of soils. Chin Pharm. 2010;21(39):3680–3.
Li XY, Xu Y, Zhang GL, Zhou M, Liu YP, Ye XD. Research Progress of Ophiopogon Japonicus. J Jiangxi Univ Tradi Chin Med. 2021;1(33):121–4.
Zhang B. The Reviews for Evolution of processed products of Chinese medicine from Ancient to Modern Times. Beijing: People’s Medical Publishing House; 1994. p. 97–100.
Wan DG, Chen L, Liu YP, Pei J, Wang GZ. Historical evolution of Polygalae Radix processing methods. J Chin Med Mater. 2005;3(28):233–6. https://doi.org/10.3321/j.issn:1001-4454.2005.03.033.
Fang MF, Fu ZhL, Wang XR, Chen H, Zhao GF, Zheng XH. Research on the senegenin composition in Polygala tenuifolia with different processing drugs method. Chin J Pharm Anal. 2009;29(3):452–7.
Chen ZhD. Query on the processing methods of Ophiopogonis Radix processed with Cinnabaris and Indigo Naturalis. Jilin J Tradit Chin Med. 1999;019(006):52. https://doi.org/10.13463/j.cnki.jlzyy.1999.06.060.
Hu ZhQ. Determination of total flavonoids in Ophiopogonis Radix and its processed products. Chin Pract Med. 2012;07(9):250–1. https://doi.org/10.3969/j.issn.1673-7555,2012.09.205.
Liu J. Research progress on pharmacological actions, toxicity and processing methods of Cinnabaris. Contem Med Symp. 2020;18(8):199–201.
Huang GW, Kang J, Dong YL, Zhang WZ. The study of aluminum toxic effect on human embryonic osteoblasts in vitro. Chin Pub Health. 2000;16(4):297–8. https://doi.org/10.3321/j.issn:1001-0580.2000.04.004.
Zhang EH, Zhao LT, Cheng Y. Experiment research on the accumulation of Alumen and aluminum in rat bone of Jiezhi capsule. J Shananxi Col Tradit Chin Med. 2008;31(6):60–2. https://doi.org/10.13424/j.cnki.jsctcm.2008.06.028.
Dong G, Wang J, Guo P, Wei D, Yang M, Kong L. Toxicity assessment of Arisaematis Rhizoma in rats by 1H NMR-based metabolomics approach. Mol BioSyst. 2014. https://doi.org/10.1039/C4MB00583J.
Feng SJ, Xia LL. Exploration on preparing methods of Hirudo. J Zhejiang Univ Tradit Chin Med. 2000;24(2):75. https://doi.org/10.3969/j.issn.1005-5509.2000.02.047.
Ma L, Ma L, OuYang LD, Wang X, Wei ZM. Study on the difference of water soluble proteins in different processed Hirudo based on SDS-PAGE. Lishizhen Med Mater Med Res. 2016;27(6):1379–81. https://doi.org/10.3969/j.issn.1008-0805.2016.06.036.
Yan WH, Cao HH, Guo Sh, Guo LY, Hu W, Cheng M, Bai DT, Chen J, Mao CQ, Li L, Lu TL. UPLC fingerprint and multi-components content determination of different processed products of Angelica sinensis. Chin J Chin Mater Med. 2019;44(12):2499–510. https://doi.org/10.19540/j.cnki.cjcmm.20190321.311.
Liu HZh, Xia XSh. Determination of the content of polysaccharides in Radix Angelicae Sinensis and its processed products. Lishizhen Med Mater Med Res. 2006;17(3):393–4. https://doi.org/10.3969/j.issn.1008-0805.2006.03.047.
This work was financially supported by grants from National Natural Science Foundation of China (No.81703675), China Postdoctoral Science Foundation (2021M692398), Natural Science Foundation of Liaoning Province (No. 2019-ZD-0631 and 2019-ZD-0914), and Dalian Municipal Medical Research Foundation (No.20Z12005).
Ethics approval and consent to participate
Consent for publication
All authors have no financial or scientific conflicts of interest with regard to the research described in this manuscript.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
The original version of this article was revised: the order of the affiliations 2 and 3 was exchanged
About this article
Cite this article
Liu, Y., Li, X., Chen, C. et al. Effect of mineral excipients on processing traditional Chinese medicines: an insight into the components, pharmacodynamics and mechanism. Chin Med 16, 143 (2021). https://doi.org/10.1186/s13020-021-00554-8
- Mineral excipients
- Traditional Chinese medicine (TCM)