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G protein-coupled receptors and traditional Chinese medicine: new thinks for the development of traditional Chinese medicine

Chinese Medicine volume 19, Article number: 92 (2024) Cite this article

Abstract

G protein-coupled receptors (GPCRs) widely exist in vivo and participate in many physiological processes, thus emerging as important targets for drug development. Approximately 30% of the Food and Drug Administration (FDA)-approved drugs target GPCRs. To date, the ‘one disease, one target, one molecule’ strategy no longer meets the demands of drug development. Meanwhile, small-molecule drugs account for 60% of FDA-approved drugs. Traditional Chinese medicine (TCM) has garnered widespread attention for its unique theoretical system and treatment methods. TCM involves multiple components, targets and pathways. Centered on GPCRs and TCM, this paper discusses the similarities and differences between TCM and GPCRs from the perspectives of syndrome of TCM, the consistency of TCM’s multi-component and multi-target approaches and the potential of GPCRs and TCM in the development of novel drugs. A novel strategy, ‘simultaneous screening of drugs and targets’, was proposed and applied to the study of GPCRs. We combine GPCRs with TCM to facilitate the modernisation of TCM, provide valuable insights into the rational application of TCM and facilitate the research and development of novel drugs. This study offers theoretical support for the modernisation of TCM and introduces novel ideas for development of safe and effective drugs.

Introduction

G protein-coupled receptors (GPCRs) widely express on the cell membrane, constituting the largest protein family encoded by the human genome [1]. G proteins can bind guanosine triphosphate (GTP) and guanosine diphosphate (GDP) and have three distinct subunits: α, β and γ [2]. They are widely distributed in various tissues and cells of the human body, participating in the regulation of body development and performing various physiological functions [3]. GPCRs are divided into five major families according to the sequence and structural similarity, namely, rhodopsin-like (class A), secretin-like (class B1), glutamate-like (class C), frizzled-like (class F) and adhesion (class B2) receptors ( Table 1). Class A has the largest proportion and the most widely studied [4] and is related to cardiovascular diseases, such as hypertension, lung diseases and mental illnesses, such as depression [5]. Class B1 GPCRs, such as glucagon-like peptide-1 receptor (GLP-1R) and glucagon receptor can regulate glucose homeostasis and lipid metabolism [6,7,8]. The Class B2 receptors are critical to the regulation of sensory, endocrine and gastrointestinal systems [9]. The physiological function of class C GPCRs has been linked to cancer, migraine, schizophrenia and movement disorders [10]. Class F GPCRs are mainly associated with cancer, fibrosis and embryonic development [11].

Table 1 Overview of GPCR subfamilies and their physiological functions
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GPCRs are the key regulators of various pathological processes and drug targets for many diseases [12], and more than 30% of FDA-approved drugs target GPCRs [13]. In 2023, ten drugs approved by the Food and Drug Administration (FDA) are related to GPCRs, which accounted for 18.2% (10/55) of the approved drugs in that year [14]. Given the considerable number of GPCR drugs approved by the FDA that year, the development and clinical application of GPCR drugs is expected to continuously expand rapidly.

Traditional Chinese medicine (TCM) compounds are used for the prevention, treatment and diagnosis of diseases, facilitate rehabilitation and have health benefits [22]. TCM usually involves multiple components, pathways, and targets, synergistically exerting its pharmacological effects [23, 24]. The theoretical framework of TCM emphasises ‘syndrome differentiation and treatment’, that is, a treatment plan is determined according to the specific physique and symptoms of a patient [25]. ‘Syndrome differentiation and treatment’ is related to the diversity of GPCRs, and the expression levels and activities of different GPCRs vary in different tissues and disease states. By studying the correlation between GPCRs and TCM syndromes, we can comprehend the regulatory mechanisms of TCM on individuals. Therefore, combining GPCRs with TCM may contribute to the modernisation of TCM.

In this paper, the advantages of the joint study of GPCRs and TCM are reviewed from the aspects of GPCRs and TCM syndromes, the characteristics of multi-component and multi-target TCM and drug screening methods. The aim is to solve problems in TCM in terms of active ingredients, molecular mechanisms, and clinical efficacy (Fig. 1). The concept of ‘Simultaneous screening of drugs and targets can clarify the characteristics and targets of drugs and is in line with the basic principles of TCM. Therefore, the research and development of TCM targeting GPCRs is considered scientific and conducive to the modernisation of TCM and international demand.

Fig. 1
figure 1

GPCRs and TCM: helping the modernisation of TCM. TCM syndromes are complex diagnostic systems, such as hyperactivity of liver-yang, which is often presented as headache and dizziness. The diversity of multi-component, multi-target, and multi-pathway TCM is consistent with GPCRs, such as KOR, GPR35 and FPR1, which are involved in the regulation of a variety of diseases and are closely related to brain injury, ulcerative colitis, and lung adenocarcinoma, respectively. CB2 cannabinoid receptor, FPR1 formyl peptide receptor 1, GPR35 G protein-coupled receptor 35, insulin-like growth KOR kappa opioid receptor, PAR1 protease-activated receptor 1, PTH1R parathyroid hormone type 1 receptor

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GPCRs and TCM syndromes: elucidating the theoretical basis and biological mechanism of TCM

The syndrome is a term exclusive to TCM and is summarised as a series of interrelated symptoms, that is, the intrinsically organic reaction state of disease location, aetiology, disease nature, disease potential and strength of the body’s disease resistance at a certain stage of the disease process, which are manifested as clinically observable symptoms.

Individualised diagnosis of TCM syndromes and diversity of GPCRs

A syndrome is a non-linear complex giant system of ‘internal reality and external deficiency’, ‘dynamic space–time’ and ‘multi-dimensional interface’ [26]. Owing to the wide variety of diseases, syndromes are constantly changing, and 2060 TCM syndromes have been identified [27]. Some syndromes are easy to distinguish, and some complex mixed and complex syndromes have been identified. Two-deficiency syndromes include the heart and kidney; heart and lung; heart and spleen; liver and kidney; and spleen and kidney. The clinical manifestations of a syndrome vary by disease. For example, in a kidney yang deficiency syndrome [28], urination can be manifested as clear and long. However, it can also be manifested as short urination or retention of urine. Kidney diseases are mostly deficiency syndromes in TCM, such as children’s nephrotic syndrome and IgA nephropathy in a certain stage of the development of the disease (like the later stage of the disease or recurrence), and can be manifested as kidney yang deficiency with six yin syndromes; clinical manifestations can be weak waist and knee, cold limbs and long urination [29] or lack of urine [30]. The complexity of TCM syndromes is the functional complexity of the same GPCRs in diseases. For example, the expression and function of the same GPCR vary by disease. CB1R is upregulated in liver fibrosis, promoting liver fibrosis [31]. However, CB1R is downregulated in colorectal cancer, and the activation of CB1R can improve rectal cancer [32]. The activation of free fatty acid receptor 4 (FFAR4), also known as G protein-coupled receptor 120, reduces atherosclerosis and protects heart function [33]. However, the activation of the FFAR4 signalling pathway can promote the growth and migration of colon cancer cells [34].

The complexity of TCM syndromes is the functional activity of the GPCR regulatory network to regulate various cell functions. The activation of GPCR regulatory subunits has shown a variety of therapeutic effects [35]. Coupling with different ligands leads to the same transduction pathway and has different relative potency, like TCM ‘same disease with different treatment’. Mogamulizumab, which acts on CXCR4, was approved by the FDA in 2012 for the treatment of relapsed or refractory adult T-cell leukaemia lymphoma [36] and in 2018 for the treatment of cutaneous T-cell lymphoma (Sezary syndrome, granuloma fungoides) [37]. Therefore, the complexity of TCM syndromes and the functional complexity of GPCRs are similar.

Dynamic changes in syndromes and GPCRs regulation

TCM syndromes are dynamic and constantly adjusted as the disease changes [38]. An untreated wind-heat surface syndrome can become an inner-heat syndrome. In an untreated wind-cold superficial syndrome, cold stagnates in the muscle surface, which can turn heat into superficial heat syndrome or become superficial cold inner heat syndrome or inner heat syndrome [39]. Similar to changes in syndromes, the downstream signals of GPCRs vary under different conditions. In the inactive state, the Gα subunit binds to guanine nucleotide GDP. Upon receptor activation, GDP is replaced by GTP, which dissociates the Gα subunit from the βγ dimer, and both subunit complexes promote intracellular effector networks, including the second messenger production system, small GTPase and kinase cascades, such as MAPK and PI3K/Akt, leading to changes in gene transcription and cellular events [40]. In addition to this regulatory process, GPCRs can migrate from the cell surface to the endosome to activate specific genes [41]. In breast cancer, which has the highest incidence among women in the world [42], for example, TCM believes that ‘stagnation of liver qi and chong-ren disorder’ is one of the core causes of breast cancer, and ‘soothing liver, tonifying kidney and promoting blood circulation’ is the most commonly used treatment method for breast cancer (Ruyan) in ancient books from the Sui Dynasty to the Qing Dynasty. During breast cancer, it experienced changes in symptoms such as liver stagnation and phlegm stagnation, late deficiency of the liver and kidney and deficiency of spleen and kidney. Along with the changes in these syndromes [43], the overexpression and abnormal activation of GPCRs participate in the development of breast cancer (Fig. 2).

Fig. 2
figure 2

Application of TCM diagnosis and GPCRs in the treatment of breast cancer. As the symptoms of breast cancer change, the composition or dosage of TCM changes. TCM products include bupleurum, poria, and white rhizoma. The FDA-approved anticancer drug motixafortide can regulate GPCRs (CXCR, STTR and GPR54) against BC. BC breast cancer, CXCR chemokine receptor, GPR54 G protein-coupled receptor 54, SSTR somatostatin receptor

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Comprehensive analysis of TCM syndrome and GPCR signal network

A syndrome is a key factor in TCM. For the syndrome of liver depression and spittoon coagulation, the liver should be cleared, qi should be regulated, phlegm should be dissolved, and formation should be dispersed. Xiaosanbei powder is added or reduced. For phlegm and blood stasis interjunction syndrome, Xiaosanbei powder combined with Xuefu Zhuyu decoction is used to reduce symptoms, and Angelica, Peach Kernel and Leonurus are added to promote blood circulation and remove blood stasis. For the liver and kidney deficiency syndrome, the Liuwei Dihuang pill combined with Gulu Erxian Dan nourishes the liver, kidneys, and marrow. In the spleen and kidney deficiency syndrome, the spleen and kidney should be strengthened. For this syndrome, Liuwei Dihuang pill combined with Sijunzi decoction can be used to reduce symptoms, along with raw turtle shell, deer horn glue and ejiao and other strong tonic drugs [44]. TCM increase or decrease drugs or change prescriptions with the change of syndrome is similar to the different effects of GPCRs binding to specific ligands in different states [45]. Lipoxin or resolvin can bind to the FPR2 receptor, inhibiting the nuclear factor κB (NF-κB) signalling pathway, upregulating the Nrf2 and peroxisome proliferator-activated receptor γ (PPARγ) signalling pathways and reducing the expression of tumour necrosis factor α (TNF-α) and interleukin 1β (IL-1β) [46, 47]. However, the FPR2 contains NF-κB binding sites. When the pro-inflammatory ligands of FPR2 (such as serum amyloid A peptide) bind to it, the NF-κB signalling pathway is activated, promoting the release of three well-known inflammatory factors: TNFα, IL-1β and IL-6 [48].

Radix bupleurum, Poria Cocos, Rhizome, Peach Kernel, Mountain Mushroom, Astragalus and Curcuma can treat breast cancer by inhibiting protease activating receptor 1 [49], chemokine receptor [50, 51], somatostatin receptor and GPR54 [52]. Therefore, the prescription can affect the development of a disease by regulating GPCRs and subtypes. CXCR4 plays a central role in tumour progression, angiogenesis, metastasis and cell survival, and its dysfunction is directly linked to various forms of cancer, often where it is not only overexpressed but also overactivated [50]. Motixafortide is the best CXCR4 antagonist, and all its alkaline residues establish interactions with residues in the CXCR4 orthosteric binding site, which seems to be the driving force behind motixafortide’s high affinity for the CXCR4 receptor [53]. Motixafortide acts on the CXCL12–CXCR4 signal axis [54] and has been used in the preclinical studies of pancreatic, breast and lung cancer [55]. Therefore, we revealed the basic theory and biological mechanism underlying TCM syndromes from the perspective of GPCRs to provide a scientific basis for the promotion of TCM.

Applying GPCRs in Chinese medicine research is beneficial to evaluating Chinese medicine mechanism

TCM often consists of various complex compounds that may act through multiple targets. Similarly, GPCRs, which constitute a large class of receptors, exhibit high structural and functional diversity. Therefore, the multiple components, targets, and pathways of TCM are consistent with the diversity of GPCRs, offering good prospects for TCM research (Fig. 3).

Fig. 3
figure 3

TCM and GPCRs, elucidating the theoretical basis and biological mechanism of TCM. a The diversity of GPCRs; b The characteristics of TCM and diseases

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Diversity of GPCRs is consistent with the multi-component and multi-target of TCM

GPCRs bind to various exogenous signalling molecules and triggering complicated intracellular signal transduction pathways [56]. This diversity is evident in the structural variances, activity characteristics and tissue- and cell-specific expression of GPCR subtypes [57]. For example, intestinal Takeda G protein-coupled receptor 5 (TGR5) promotes the secretion of glucagon-like peptide-1 (GLP-1) [58] and regulates blood sugar by acting on intestinal L cells. Additionally, TGR5 in adipocytes enhances brown adipose tissue function and induces white adipose tissue browning by regulating the expression of genes associated with glucose, fatty acid, and cholesterol homeostasis [59]. The activation of GPR35 can induce ATP synthase dimerization, reducing ATP loss during ischemia and preventing cerebral ischemia injury [60]. However, GPR35 serves as an early marker of heart failure because it is upregulated in the myocardial tissues of patients with heart failure [61]. GPR35 knockout can relieve hypertension induced by angiotensin II [62] and deoxycorticosterone acetate [63]. These studies demonstrated the complexity and functional diversity of GPCRs.

TCM often comprises complex compounds extracted from various natural plants, possessing diverse biological activities, and affecting multiple targets [64]. In contrast to the single-molecule targeted therapy of Western medicine, Chinese medicine emphasises overall regulation, achieving coordinated cellular and organ functions through the actions of multiple components and targets [65]. Rhodiola crenulate and its main component, salidroside, can prevent and treat brain injury at high altitudes through the ‘brain–lung’ axis [66]. Berberine from Coptis Chinensis can act on EIF2AK2, nucleic acids, gut microbiota and MAPK and exert anti-inflammatory pharmacological effects [67]. Notably, berberine can improve rat kidney injury caused by G protein-coupled receptor kinases [68]. Furthermore, bitter, sweet and olfactory receptors are also GPCRs [69]. Xuanfeibaidu granules can inhibit COVID-19 through ACE2 [65, 70, 71]. Verbenalin derived from Verbena can improve acute lung injury by targeting GPR18 [72]. These findings demonstrated the consistency between GPCRs and TCM characteristics, indicating that many TCM compounds exert pharmacological effects through GPCRs or GPCR-mediated signalling pathways.

Characteristics of TCM and current multi-target drug development

Drug development is based on the idea ‘one disease, one target, one molecule’. However, the pathogenesis of most diseases is complex and diverse, and even the symptoms of the same disease vary. Consequently, drugs that target a single target are often struggling to meet treatment needs [73]. Initially, researchers believed that artemisinin targets only sarcoplasmic-endoplasmic reticulum calcium ATPase (SERCA) to combat malaria [74]; however, domestic researchers later discovered that artemisinin interacts with 124 targets [75], including GPCRs. These interactions provide the molecular basis for the multi-component and multi-target characteristics of TCM. A deep understanding of the interactions between active ingredients and GPCRs in Chinese herbs can provide insights for discovering novel and precise drug targets.

In contrast to a single drug that targets a single GPCR, TCM and herbal compounds often contain multiple components that may simultaneously affect multiple GPCR subtypes. This holistic regulation aligns more closely with the concept of the ‘holistic view’ of TCM, that is, the comprehensive treatment of diseases through multi-pathway and multi-level intervention [76]. For instance, Qingre Jiangzhuo prescription, a heat-clearing and detoxification compound, may regulate immune and inflammatory responses by targeting GPR119 and GLP-1R [77]. Associating GPCRs with TCM can enhance the efficiency of drug research and development. Understanding the multi-component and multi-target characteristics of TCM can facilitate the design and screening of candidate drug compounds with specificity and reduces the time and cost of drug research and development.

GPCRs help in the discovery of new targeted TCM or drugs

Several screening methods for GPCRs have been proposed, including high-throughput screening (HTS), structure-based virtual screening, protein–small molecule interaction-based affinity mass spectrometry and cell membrane chromatography (CMC; Fig. 4). These methods offer potential compounds for discovering novel drugs. For instance, anti-allergic asthma lead compounds were explored through Mas-related G protein-coupled receptor-X2 (MrgX2) CMC, targeting the mast cell MRGPRX2 [78]; natural products, such as diamine, shikotin and acetylshikotin, exhibited promising effects on asthma [79]. The three current screening methods are outlined below.

Fig. 4
figure 4

Commonly used GPCRs screening methods. a Virtual filtering based on structure; b HTS; c screening techniques based on proteins and small molecules

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High-throughput screening (HTS)

HTS is a critical technique in drug discovery and identification of potential candidates for pharmacological optimisation from compound libraries [80]. This technology integrates pharmacology, molecular biology, cell biology, computer technology and automatic control technology for rapid, efficient, micro-quantitative, automated, and scalable drug screening. Cell-based screening techniques include stable strain, CRISPR activation (CRISPRa) and CRISPR interference (CRISPRi) [81]. CRISPRa and CRISPRi have been utilised in screening autoimmune diseases and cancer, revealing genes that reprogram critical immune cell functions and informing the design of immunotherapies [82]. Additionally, the PRESTO-Salsa HTS platform with mRNA barcode technology as the core has successfully screened GPCR agonists [83]. Veozah [14], which was approved by the FDA in 2023, was obtained through HTS screening with subsequent structure optimisation.

Virtual filtering based on structure

Structure-based virtual screening has been widely utilised to discover active molecules targeting various therapeutic targets [84]. Chemical and protein datasets with rich bioactivity data have been obtained [85]. Artificial intelligence, especially machine learning methods, including deep learning, has successfully utilised these datasets for the construction of score functions necessary for the virtual screening of targets with information about three-dimensional atomic structure [86]. These target-specific machine learning scoring functions are generally superior to traditional generality scoring functions, representing the latest advances in structure-based virtual screening techniques. For example, through structure-based virtual screening of 16 FDA-approved drugs against ROCK1, researchers have identified dasabuvir, which is a drug used to treat hepatitis C virus infection, as a potential drug for treating human enterovirus class A infection [87]. Our research group review clarified the flow of AI in GPCR ligand discovery. Using artificial intelligence, we have gained novel insights into complex TCM components and diverse GPCRs [88], thereby paving the way for the development of innovative therapies for a wide range of diseases.

Screening techniques based on proteins and small molecules

The method based on protein–small molecule interaction has been successfully applied to screening ligands for various soluble drug target proteins. It is closely integrated with biochemical and cell function experiments, demonstrating high potential as a tool for discovering novel lead compounds and revealing novel targets within key signal transduction pathways [89]. Affinity mass spectrometry can efficiently and rapidly screen 28 potential ligands from a pool of 20,000 compounds, leading to the discovery of three new adenosine A2A receptor antagonists [90]. Additionally, 12 small-molecule regulators of 5-HT2CR and several previously unknown structural ligands have been identified by screening 4333 compounds [91]. These newly discovered ligands affect appetite and alleviate obesity, and four novel structural agonists specifically targeting GLP-1R have been discovered [92]. These findings suggest that affinity mass spectrometry play a prominent role in the screening of natural active compounds for protein targeting and in the regulation of protein function through intracellular metabolites. CMC and affinity mass spectrometry share the same principle. Therefore, utilising protein–small molecule interaction to target and screen the potential ligands of GPCRs is crucial for the development of novel drugs and exploration of pharmacological mechanisms.

Concept of ‘simultaneous screening of drugs and targets’

The research strategy of Western medicine is usually based on target screening. Referencing the above several screening methods combined with the characteristics of TCM and GPCRs, we proposed a new screening strategy, ‘Simultaneous screening of drugs and targets’. This approach entails the concurrent screening of drugs and their potential targets. In brief, (1) disease targets are obtained with animal disease models or clinical data. (2) Known targets (e.g., HER2 for breast cancer [93]) and potential compounds in TCM or Chinese medicine compounds are screened. For example, nuclear receptor PXR is the target of autoimmune hepatitis [94], and PXR is used as a target for screening potential ligands from compound libraries or TCM. The general steps are as follows: disease targets are obtained through disease databases or experiments for receptor identification. Based on the principle of receptor action, the indirect screening of drugs is conducted, and the effects of drugs on receptors are assessed according to subsequent changes in biological effects after receptor activation. The aim is to provide an optimal therapeutic effect or personalised drugs for individual patients [95]. Additionally, direct screening is carried out to determine the target of action and the pathway of action by detecting the ability of a receptor to bind with a drug, thereby reflecting their interaction [96]. Utilising our statistical compound library of TCM and our GPCR target library, we conducted many-to-many virtual screenings to delineate the range of compounds. Subsequently, the selection was refined by subjecting the stable transmutation strain library to HTS [97, 98] followed by in vivo and in vitro experiments for verifying the efficacy of drugs and their action targets.

Conclusion

The TCM syndrome and TCM emphasises individual differences and holistic concepts, and the expression levels and activity of GPCRs can vary among individuals. A study of the relationship between GPCRs and TCM is helpful to the realisation of personalised medicine therapy. Detailed information about a patient’s TCM syndromes and the status of relevant GPCRs facilitates the selection of a suitable drug regimen. Integrating TCM with modern drug research and development will facilitate the modernisation of TCM. Exploring the pharmacological mechanisms of TCM and combining them with advanced biotechnological methods are essential to the development of safe and effective drugs and establishment of a robust foundation for the integration of TCM into modern medicine.

The utilisation of TCM is limited because of its complex composition and unclear mechanism of action. Many GPCR drugs suffer from low specificity and high toxic side effects, thus limiting their effectiveness. The unstable structure and low expression of GPCR targets impedes the isolation of GPCRs. Therefore, the establishment of a standardised and widely applicable GPCR drug screening platform is a crucial step towards the advancement and modernisation of TCM. We aim to develop a comprehensive screening platform and cell library for GPCRs to promote the development of TCM and facilitate further research on GPCRs.

In summary, TCM treats different diseases with the same origin and employs the same treatment for different diseases, analogous to the concept of ‘simultaneous screening of drugs and targets’. Moreover, GPCRs are closely associated with TCM, and the fundamental theory and biological mechanisms of TCM can be elucidated by investigating TCM syndromes through GPCRs. The multi-component and multi-target characteristics of TCM align with the diversity of GPCRs, providing robust support for TCM scientific research and novel drug development. Further exploration of the relationship between GPCRs and Chinese medicine holds significant promise for the advancement and modernisation of TCM, personalised treatment and drug research and development. In conclusion, multi-target drug development is aligned more with the needs of complex diseases and contemporary drug development.

Data availability

All data generated or analysed during this study are published article.

Abbreviations

ATL:

Adult T-cell leukaemia lymphoma

BC:

Breast cancer

CB2R:

Cannabinoid receptor 2

class A:

Rhodopsin-like receptors

class B1:

Secretin-like receptors

class B2/aGPCR:

Adhesion-like receptor

class C:

Glutamate-like receptors

class F:

 Frizzled-like

CMC:

Cell membrane chromatography

CRISPRa:

CRISPR activation

CRISPRi:

CRISPR interference

CXCR:

Chemokine receptor

FDA:

Food and Drug Administration

FFAR4:

Free fatty acid receptor 4

FPR1:

Formyl peptide receptor 1

GCGR:

Glucagon receptor

GLP-1R:

Glucagon-like peptide-1 receptor

GPCRs:

G protein-coupled receptors

GPR35:

G protein-coupled receptor 35

GPR54:

G protein-coupled receptor 54

GRKs:

G protein-coupled receptor kinases

HTS:

High-throughput screening

IL-1β:

Interleukin 1β

KOR:

Kappa opioid receptor

MrgX2:

Mas-related G protein-coupled receptor-X2

NF-κB:

Nuclear factor κB

PAR1:

Protease-activating receptor 1

PTH1R:

Parathyroid hormone type 1 receptor

SSTR:

Somatostatin receptor

TCM:

Traditional Chinese medicine

TNF-α:

Tumour necrosis factor α

References

  1. Masuho I, Kise R, Gainza P, Von Moo E, Li X, Tany R, et al. Rules and mechanisms governing G protein coupling selectivity of GPCRs. Cell Rep. 2023;42(10): 113173.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Rosenbaum DM, Rasmussen SG, Kobilka BK. The structure and function of G-protein-coupled receptors. Nature. 2009;459(7245):356–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Janetzko J, Kise R, Barsi-Rhyne B, Siepe DH, Heydenreich FM, Kawakami K, et al. Membrane phosphoinositides regulate GPCR-β-arrestin complex assembly and dynamics. Cell. 2022;185(24):4560-4573.e4519.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Foster SR, Hauser AS, Vedel L, Strachan RT, Huang X-P, Gavin AC, et al. Discovery of human signaling systems: pairing peptides to G protein-coupled receptors. Cell. 2019;179(4):895-908.e821.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Yang D, Zhou Q, Labroska V, Qin S, Darbalaei S, Wu Y, et al. G protein-coupled receptors: structure-and function-based drug discovery. Signal Transduct Target Ther. 2021;6(1):7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Yu M, Benjamin MM, Srinivasan S, Morin EE, Shishatskaya EI, Schwendeman SP, et al. Battle of GLP-1 delivery technologies. Adv Drug Deliv Rev. 2018;130:113–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Williams DM, Nawaz A, Evans M. Drug therapy in obesity: a review of current and emerging treatments. Diabetes Ther. 2020;11(6):1199–216.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Zhang M, Chen T, Lu X, Lan X, Chen Z, Lu S. G protein-coupled receptors (GPCRs): advances in structures, mechanisms, and drug discovery. Signal Transduct Target Ther. 2024;9(1):88.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Bondarev AD, Attwood MM, Jonsson J, Chubarev VN, Tarasov VV, Schiöth HB. Opportunities and challenges for drug discovery in modulating adhesion G protein-coupled receptor (GPCR) functions. Expert Opin Drug Discov. 2020;15(11):1291–307.

    Article  CAS  PubMed  Google Scholar 

  10. Pin JP, Kniazeff J, Liu J, Binet V, Goudet C, Rondard P, et al. Allosteric functioning of dimeric class CG-protein-coupled receptors. FEBS J. 2005;272(12):2947–55.

    Article  CAS  PubMed  Google Scholar 

  11. Schulte G, Wright SC. Frizzleds as GPCRs—more conventional than we thought! Trends Pharmacol Sci. 2018;39(9):828–42.

    Article  CAS  PubMed  Google Scholar 

  12. Qu X, Wang D, Wu B. Progress in GPCR structure determination. In: GPCRs. London: Elsevier; 2020. p. 3–22.

    Chapter  Google Scholar 

  13. Hauser AS, Attwood MM, Rask-Andersen M, Schiöth HB, Gloriam DE. Trends in GPCR drug discovery: new agents, targets and indications. Nat Rev Drug Discov. 2017;16(12):829–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Mullard A. 2023 FDA approvals. Nat Rev Drug Discov. 2024;23(2):88–95.

    Article  CAS  PubMed  Google Scholar 

  15. Zhang H, Han GW, Batyuk A, Ishchenko A, White KL, Patel N, et al. Structural basis for selectivity and diversity in angiotensin II receptors. Nature. 2017;544(7650):327–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Jialu W, Clarice G, Howard AR. G-Protein-coupled receptors in heart disease. Circ Res. 2018;123(6):716–35.

    Article  Google Scholar 

  17. Da Young O, Evelyn W, Taro EA, William SL, Denise EL, Ariane P, et al. A Gpr120-selective agonist improves insulin resistance and chronic inflammation in obese mice. Nat Med. 2014;20(8):942–7.

    Article  Google Scholar 

  18. Randy AH, Trisha L. Adhesion G protein-coupled receptors: structure, signaling, physiology, and pathophysiology. Physiol Rev. 2022;102(4):1587–624.

    Article  Google Scholar 

  19. Dongchen Y, Jing H, Xiaoman J, Eva Maria P, Simin Z, Stephane K, et al. NMDAR antagonists suppress tumor progression by regulating tumor-associated macrophages. Proc Natl Acad Sci USA. 2023;120(47): e2302126120.

    Article  Google Scholar 

  20. Huang L, Xiao W, Wang Y, Li J, Gong J, Tu E, et al. Metabotropic glutamate receptors (mGluRs) in epileptogenesis: an update on abnormal mGluRs signaling and its therapeutic implications. Neural Regen Res. 2024;19(2):360–8.

    Article  CAS  PubMed  Google Scholar 

  21. Shaoqin Z, Jiahui L, Zhongqiu P, Hui Z, Yinuo W, Lanjing M, et al. Aberrant cholesterol metabolism and Wnt/β-catenin signaling coalesce via frizzled5 in supporting cancer growth. Adv Sci. 2022;9(28): e2200750.

    Article  Google Scholar 

  22. Tang JL, Liu BY, Ma KW. Traditional Chinese medicine. Lancet. 2008;372(9654):1938–40.

    Article  PubMed  Google Scholar 

  23. Li X, Liu Z, Liao J, Chen Q, Lu X, Fan X. Network pharmacology approaches for research of traditional Chinese medicines. Chin J Nat Med. 2023;21(5):323–32.

    PubMed  Google Scholar 

  24. Liu Y, Li X, Chen C, Ding N, Zheng P, Chen X, et al. TCMNPAS: a comprehensive analysis platform integrating network formulaology and network pharmacology for exploring traditional Chinese medicine. Chin Med. 2024;19(1):50.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Tang Y, Li Z, Yang D, Fang Y, Gao S, Liang S, et al. Research of insomnia on traditional Chinese medicine diagnosis and treatment based on machine learning. Chin Med. 2021;16(1):2.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Guo L, Wang Y-Y. Study thoughts on complex phenomena in syndrome of Chinese Meelicine. Chin J Basic Med Tradit Chin Med. 2004;10(2):3–12.

    Google Scholar 

  27. Hongyong D, Adams CE, Shokraneh F, Shanghua L. Classification of interventions in traditional Chinese medicine. J Tradit Chin Med. 2018;38(2):315–20.

    Article  Google Scholar 

  28. Chen R, Wang J, Zhan R, Zhang L, Wang X. Fecal metabonomics combined with 16S rRNA gene sequencing to analyze the changes of gut microbiota in rats with kidney-yang deficiency syndrome and the intervention effect of You-gui pill. J Ethnopharmacol. 2019;244: 112139.

    Article  CAS  PubMed  Google Scholar 

  29. Zheng J. Traditional Chinese medicine clinical thinking based on the combination of disease and syndrome. Tradit Chin Med. 2021;10(2):246–50.

    Article  Google Scholar 

  30. Mei Chen JS. Research progress of traditional chinese medicine in treating IgA nephropathy through notch signaling pathway. MEDS Chin Med. 2023;5(8):1–8.

    Google Scholar 

  31. Teixeira-Clerc F, Julien B, Grenard P, Van Nhieu JT, Deveaux V, Li L, et al. CB1 cannabinoid receptor antagonism: a new strategy for the treatment of liver fibrosis. Nat Med. 2006;12(6):671–6.

    Article  CAS  PubMed  Google Scholar 

  32. Wang D, Wang H, Ning W, Backlund MG, Dey SK, DuBois RN. Loss of cannabinoid receptor 1 accelerates intestinal tumor growth. Cancer Res. 2008;68(15):6468–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Stuttgen GM, Sahoo D. FFAR4: a new player in cardiometabolic disease? Endocrinology. 2021;162(8): bqa111.

    Article  Google Scholar 

  34. Takahashi K, Fukushima K, Onishi Y, Minami K, Otagaki S, Ishimoto K, et al. Involvement of FFA1 and FFA4 in the regulation of cellular functions during tumor progression in colon cancer cells. Exp Cell Res. 2018;369(1):54–60.

    Article  CAS  PubMed  Google Scholar 

  35. Prömel S, Langenhan T, Araç D. Matching structure with function: the GAIN domain of adhesion-GPCR and PKD1-like proteins. Trends Pharmacol Sci. 2013;34(8):470–8.

    Article  PubMed  Google Scholar 

  36. Yonekura K, Kusumoto S, Choi I, Nakano N, Ito A, Suehiro Y, et al. Mogamulizumab for adult T-cell leukemia-lymphoma: a multicenter prospective observational study. Blood Adv. 2020;4(20):5133–45.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Kim YH, Bagot M, Pinter-Brown L, Rook AH, Porcu P, Horwitz SM, et al. Mogamulizumab versus vorinostat in previously treated cutaneous T-cell lymphoma (MAVORIC): an international, open-label, randomised, controlled phase 3 trial. Lancet Oncol. 2018;19(9):1192–204.

    Article  CAS  PubMed  Google Scholar 

  38. Lo V. Huangdi Hama jing (Yellow emperor’s toad canon). Asia Major. 2001;14(2):61–99.

    Google Scholar 

  39. Jung W-J, Baik Y, Yoon E, Jung H-S. The motive for dissection and the view of the body in the yellow emperor’s inner classic (Huangdineijing). Oriental Pharm Exp Med. 2018;18:21–31.

    Article  CAS  Google Scholar 

  40. Cvicek V, Goddard WA III, Abrol R. Structure-based sequence alignment of the transmembrane domains of all human GPCRs: phylogenetic, structural and functional implications. PLoS Comput Biol. 2016;12(3): e1004805.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Bowman SL, Shiwarski DJ, Puthenveedu MA. Distinct G protein-coupled receptor recycling pathways allow spatial control of downstream G protein signaling. J Cell Biol. 2016;214(7):797–806.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394–424.

    Article  PubMed  Google Scholar 

  43. Ernestina DF, Federica S, Robert C, Michael L, Marcello M. G Protein-coupled receptors at the crossroad between physiologic and pathologic angiogenesis: old paradigms and emerging concepts. Int J Mol Sci. 2017;18(12):2713.

    Article  Google Scholar 

  44. Chen Q, Pei X. Consensus on TCM syndrome differentiation and internal therapy for early-stage breast cancer. J Beijing Univ Trad Chin Med (Clin Med). 2020;27(3):5–8.

    Google Scholar 

  45. Lappano R, Jacquot Y, Maggiolini M. GPCR modulation in breast cancer. Int J Mol Sci. 2018;19(12):3840.

    Article  PubMed  PubMed Central  Google Scholar 

  46. Petri MH, Thul S, Andonova T, Lindquist-Liljeqvist M, Jin H, Skenteris NT, et al. Resolution of inflammation through the lipoxin and ALX/FPR2 receptor pathway protects against abdominal aortic aneurysms. JACC Basic Transl Sci. 2018;3(6):719–27.

    Article  PubMed  PubMed Central  Google Scholar 

  47. Su CJ, Zhang JT, Zhao FL, Xu DL, Pan J, Liu T. Resolvin D1/N-formyl peptide receptor 2 ameliorates paclitaxel-induced neuropathic pain through the activation of IL-10/Nrf2/HO-1 pathway in mice. Front Immunol. 2023;14:1091753.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. De Buck M, Gouwy M, Wang JM, Van Snick J, Proost P, Struyf S, et al. The cytokine-serum amyloid A-chemokine network. Cytokine Growth Factor Rev. 2016;30:55–69.

    Article  PubMed  Google Scholar 

  49. Singh A, Nunes JJ, Ateeq B. Role and therapeutic potential of G-protein coupled receptors in breast cancer progression and metastases. Eur J Pharmacol. 2015;763:178–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Wescott MP, Kufareva I, Paes C, Goodman JR, Thaker Y, Puffer BA, et al. Signal transmission through the CXC chemokine receptor 4 (CXCR4) transmembrane helices. Proc Natl Acad Sci. 2016;113(35):9928–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Dalm SU, Sieuwerts AM, Look MP, Melis M, van Deurzen CH, Foekens JA, et al. Clinical relevance of targeting the gastrin-releasing peptide receptor, somatostatin receptor 2, or chemokine CXC motif receptor 4 in breast cancer for imaging and therapy. J Nucl Med. 2015;56(10):1487–93.

    Article  CAS  PubMed  Google Scholar 

  52. Papaoiconomou E, Lymperi M, Petraki C, Philippou A, Msaouel P, Michalopoulou F, et al. Kiss-1/GPR54 protein expression in breast cancer. Anticancer Res. 2014;34(3):1401–7.

    PubMed  Google Scholar 

  53. Rebolledo-Bustillo M, Garcia-Gomez D, Dávila EM, Castro ME, Caballero NA, Melendez FJ, et al. Structural basis of the binding mode of the antineoplastic compound motixafortide (BL-8040) in the CXCR4 chemokine receptor. Int J Mol Sci. 2023;24(5):4393.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Crees ZD, Stockerl-Goldstein K, Vainstein A, Chen H, DiPersio JF. GENESIS: phase III trial evaluating BL-8040+ G-CSF to mobilize hematopoietic cells for autologous transplant in myeloma. Future Oncol. 2019;15(31):3555–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Bockorny B, Semenisty V, Macarulla T, Borazanci E, Wolpin BM, Stemmer SM, et al. BL-8040, a CXCR4 antagonist, in combination with pembrolizumab and chemotherapy for pancreatic cancer: the COMBAT trial. Nat Med. 2020;26(6):878–85.

    Article  CAS  PubMed  Google Scholar 

  56. Tehan BG, Bortolato A, Blaney FE, Weir MP, Mason JS. Unifying family A GPCR theories of activation. Pharmacol Ther. 2014;143(1):51–60.

    Article  CAS  PubMed  Google Scholar 

  57. Wang J, Hua T, Liu ZJ. Structural features of activated GPCR signaling complexes. Curr Opin Struct Biol. 2020;63:82–9.

    Article  CAS  PubMed  Google Scholar 

  58. Pathak P, Xie C, Nichols RG, Ferrell JM, Boehme S, Krausz KW, et al. Intestine farnesoid X receptor agonist and the gut microbiota activate G-protein bile acid receptor-1 signaling to improve metabolism. Hepatology. 2018;68(4):1574–88.

    Article  CAS  PubMed  Google Scholar 

  59. Fan M, Wang Y, Jin L, Fang Z, Peng J, Tu J, et al. Bile acid-mediated activation of brown fat protects from alcohol-induced steatosis and liver injury in mice. Cell Mol Gastroenterol Hepatol. 2022;13(3):809–26.

    Article  CAS  PubMed  Google Scholar 

  60. Wyant GA, Yu W, Doulamis IP, Nomoto RS, Saeed MY, Duignan T, et al. Mitochondrial remodeling and ischemic protection by G protein-coupled receptor 35 agonists. Science. 2022;377(6606):621–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Min KD, Asakura M, Liao Y, Nakamaru K, Okazaki H, Takahashi T, et al. Identification of genes related to heart failure using global gene expression profiling of human failing myocardium. Biochem Biophys Res Commun. 2010;393(1):55–60.

    Article  CAS  PubMed  Google Scholar 

  62. Wang W, Han T, Tong W, Zhao J, Qiu X. Overexpression of GPR35 confers drug resistance in NSCLC cells by β-arrestin/Akt signaling. Onco Targets Ther. 2018;11:6249–57.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Guo YJ, Zhou YJ, Yang XL, Shao ZM, Ou ZL. The role and clinical significance of the CXCL17-CXCR8 (GPR35) axis in breast cancer. Biochem Biophys Res Commun. 2017;493(3):1159–67.

    Article  CAS  PubMed  Google Scholar 

  64. Wang M, Yin F, Kong L, Yang L, Sun H, Sun Y, et al. Chinmedomics: a potent tool for the evaluation of traditional Chinese medicine efficacy and identification of its active components. Chin Med. 2024;19(1):47.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Huang K, Zhang P, Zhang Z, Youn JY, Wang C, Zhang H, et al. Traditional Chinese medicine (TCM) in the treatment of COVID-19 and other viral infections: efficacies and mechanisms. Pharmacol Ther. 2021;225: 107843.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Xie N, Fan F, Jiang S, Hou Y, Zhang Y, Cairang N, et al. Rhodiola crenulate alleviates hypobaric hypoxia-induced brain injury via adjusting NF-κB/NLRP3-mediated inflammation. Phytomedicine. 2022;103: 154240.

    Article  CAS  PubMed  Google Scholar 

  67. Ai X, Yu P, Luo L, Sun J, Tao H, Wang X, et al. Berberis dictyophylla F. inhibits angiogenesis and apoptosis of diabetic retinopathy via suppressing HIF-1α/VEGF/DLL-4/Notch-1 pathway. J Ethnopharmacol. 2022;296: 115453.

    Article  CAS  PubMed  Google Scholar 

  68. Wang FL, Tang LQ, Yang F, Zhu LN, Cai M, Wei W. Renoprotective effects of berberine and its possible molecular mechanisms in combination of high-fat diet and low-dose streptozotocin-induced diabetic rats. Mol Biol Rep. 2013;40(3):2405–18.

    Article  CAS  PubMed  Google Scholar 

  69. Xu W, Wu L, Liu S, Liu X, Cao X, Zhou C, et al. Structural basis for strychnine activation of human bitter taste receptor TAS2R46. Science. 2022;377(6612):1298–304.

    Article  CAS  PubMed  Google Scholar 

  70. Niu W, Wu F, Cui H, Cao W, Chao Y, Wu Z, et al. Network pharmacology analysis to identify phytochemicals in traditional Chinese Medicines that may regulate ACE2 for the treatment of COVID-19. Evid Based Complement Alternat Med. 2020;2020:7493281.

    Article  PubMed  PubMed Central  Google Scholar 

  71. Leng L, Xu Z, Hong B, Zhao B, Tian Y, Wang C, et al. Cepharanthine analogs mining and genomes of Stephania accelerate anti-coronavirus drug discovery. Nat Commun. 2024;15(1):1537.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Yang L, Liu T, Zhuo Y, Li D, Li D, Liu J, et al. Verbenalin alleviates acute lung injury induced by sepsis and IgG immune complex through GPR18 receptor. Cell Signal. 2023;109: 110768.

    Article  CAS  PubMed  Google Scholar 

  73. Chen Z, Yu J, Wang H, Xu P, Fan L, Sun F, et al. Flexible scaffold-based cheminformatics approach for polypharmacological drug design. Cell. 2024;187(9):2194–208.

    Article  CAS  PubMed  Google Scholar 

  74. Valderramos SG, Scanfeld D, Uhlemann AC, Fidock DA, Krishna S. Investigations into the role of the Plasmodium falciparum SERCA (PfATP6) L263E mutation in artemisinin action and resistance. Antimicrob Agents Chemother. 2010;54(9):3842–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Wang J, Zhang CJ, Chia WN, Loh CC, Li Z, Lee YM, et al. Haem-activated promiscuous targeting of artemisinin in Plasmodium falciparum. Nat Commun. 2015;6:10111.

    Article  CAS  PubMed  Google Scholar 

  76. Dong J, Lu L, Le J, Yan C, Zhang H, Li L. Philosophical thinking of Chinese traditional medicine. Tradit Med Modern Med. 2018;1(01):1–10.

    Article  CAS  Google Scholar 

  77. Liu W. The mechanism of Qingrejiangzhuo decotion in promoting Glucagon-like peptide 1 secretion through regulating the expression of G-protein coupled receptor 119. Beijing: China Academy of Chinese Medical Sciences; 2013. p. 1–177.

    Google Scholar 

  78. Jia Q, Fu J, Gao C, Wang H, Wang S, Liang P, et al. MrgX2-SNAP-tag/cell membrane chromatography model coupled with liquid chromatography-mass spectrometry for anti-pseudo-allergic compound screening in Arnebiae Radix. Anal Bioanal Chem. 2022;414(19):5741–53.

    Article  CAS  PubMed  Google Scholar 

  79. Liu R, Hu S, Ding Y, Wang J, Wang Y, Gao J, et al. Dictamnine is an effective anti-anaphylactoid compound acting via the MrgX2 receptor located on mast cells. Phytother Res. 2021;35(6):3181–93.

    Article  CAS  PubMed  Google Scholar 

  80. Zhang R, Xie X. Tools for GPCR drug discovery. Acta Pharmacol Sin. 2012;33(3):372–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Jensen TI, Mikkelsen NS, Gao Z, Foßelteder J, Pabst G, Axelgaard E, et al. Targeted regulation of transcription in primary cells using CRISPRa and CRISPRi. Genome Res. 2021;31(11):2120–30.

    Article  PubMed  PubMed Central  Google Scholar 

  82. Schmidt R, Steinhart Z, Layeghi M, Freimer JW, Bueno R, Nguyen VQ, et al. CRISPR activation and interference screens decode stimulation responses in primary human T cells. Science. 2022;375(6580): eabj4008.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Chen H, Rosen CE, González-Hernández JA, Song D, Potempa J, Ring AM, et al. Highly multiplexed bioactivity screening reveals human and microbiota metabolome-GPCRome interactions. Cell. 2023;186(14):3095-3110.e3019.

    Article  PubMed  Google Scholar 

  84. Ballante F, Kooistra AJ, Kampen S, de Graaf C, Carlsson J. Structure-based virtual screening for ligands of G protein-coupled receptors: what can molecular docking do for you? Pharmacol Rev. 2021;73(4):527–65.

    Article  PubMed  Google Scholar 

  85. Nguyen ATN, Nguyen DTN, Koh HY, Toskov J, MacLean W, Xu A, et al. The application of artificial intelligence to accelerate G protein-coupled receptor drug discovery. Br J Pharmacol. 2023. https://doi.org/10.1111/bph.16140.

    Article  PubMed  Google Scholar 

  86. Chen W, Liu X, Zhang S, Chen S. Artificial intelligence for drug discovery: resources, methods, and applications. Mol Ther Nucleic Acids. 2023;31:691–702.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Zhao X, Li C, Chiu MC, Qiao R, Jiang S, Wang P, et al. Rock1 is a novel host dependency factor of human enterovirus A71: implication as a drug target. J Med Virol. 2022;94(11):5415–24.

    Article  CAS  PubMed  Google Scholar 

  88. Chen W, Song C, Leng L, Zhang S, Chen S. The application of artificial intelligence accelerates G protein-coupled receptor ligand discovery. Engineering. 2023;32:18–28.

    Article  Google Scholar 

  89. Prokai L, Zaman K, Prokai-Tatrai K. Mass spectrometry-based retina proteomics. Mass Spectrom Rev. 2023;42(3):1032–62.

    Article  CAS  PubMed  Google Scholar 

  90. Lu Y, Qin S, Zhang B, Dai A, Cai X, Ma M, et al. Accelerating the throughput of affinity mass spectrometry-based ligand screening toward a G protein-coupled receptor. Anal Chem. 2019;91(13):8162–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Zhang B, Zhao S, Yang D, Wu Y, Xin Y, Cao H, et al. A novel G protein-biased and subtype-selective agonist for a G protein-coupled receptor discovered from screening herbal extracts. ACS Cent Sci. 2020;6(2):213–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Yuan S, Xia L, Wang C, Wu F, Zhang B, Pan C, et al. Conformational dynamics of the activated GLP-1 receptor-G(s) complex revealed by cross-linking mass spectrometry and integrative structure modeling. ACS Cent Sci. 2023;9(5):992–1007.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Takada M, Toi M. Neoadjuvant treatment for HER2-positive breast cancer. Chin Clin Oncol. 2020;9(3):32.

    Article  PubMed  Google Scholar 

  94. Zhang T, Rao Q, Dai M, Wu ZE, Zhao Q, Li F. Tripterygium wilfordii protects against an animal model of autoimmune hepatitis. J Ethnopharmacol. 2023;309: 116365.

    Article  CAS  PubMed  Google Scholar 

  95. Kim D, Kim SB, Ryu JL, Hong H, Chang JH, Yoo TJ, et al. Human embryonic stem cell-derived Wilson’s disease model for screening drug efficacy. Cells. 2020;9(4):872.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Gong K, Guo W, Du K, Wang F, Li M, Guo J. Mechanism of huoluo xiaoling dan in the treatment of psoriasis based on network pharmacology and molecular docking. Evid-Based Complement Altern Med. 2022;2022:7053613.

    Google Scholar 

  97. Zhang Z, Wang G, Zhong K, Chen Y, Yang N, Lu Q, et al. A drug screening to identify novel combinatorial strategies for boosting cancer immunotherapy efficacy. J Transl Med. 2023;21(1):23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Lee SY, Hwang HJ, Ku B, Lee DW. Cell proliferation receptor-enhanced 3D high-throughput screening model for optimized drug efficacy evaluation in breast cancer cells. Anal Chem. 2022;94(34):11838–47.

    Article  CAS  PubMed  Google Scholar 

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Funding

This work was supported by grant from the Post-Doctor Research Project, Chengdu University of Traditional Chinese Medicine (BSZ2023064).

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Authors and Affiliations

  1. Institute of Herbgenomics, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China

    Ting Zhang, Shengjie You & Shilin Chen

  2. Innovative Institute of Chinese Medicine and Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611100, China

    Ting Zhang, Wenqiao An & Sanyin Zhang

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  1. Ting Zhang
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Ting Zhang: conceived, designed, wrote, and revised the manuscript. Wenqiao An: wrote and revised the manuscript. Shengjie You: revised the manuscript, Sanyin Zhang and Shilin Chen: contributed to the revision of the manuscript.

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Zhang, T., An, W., You, S. et al. G protein-coupled receptors and traditional Chinese medicine: new thinks for the development of traditional Chinese medicine. Chin Med 19, 92 (2024). https://doi.org/10.1186/s13020-024-00964-4

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Chinese Medicine

ISSN: 1749-8546

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