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Table 1 Information of natural anti-complement products and results of in vitro and in vivo activities

From: Natural products provide a new perspective for anti-complement treatment of severe COVID-19: a review

Pharmacology activity

Source

In vitro anti-complementary activity

In vivo treatment of diseases associated with abnormal activation of complement

Crude Arnebiaeuchroma polysaccharides (CAEP)

Arnebia euchroma (Royle) I.M.Johnst

CH50 = 0.397 ± 0.011 mg/mL (CAEP)

CAEP treatment ameliorated febrile response and ALI induced by LPS or LPS plus ischemia reperfusion in rats, through attenuating the morphological injury, edema, and permeability in the lung and weakening the oxidant stress in BALF. CAEP treatment also improved the level of complement and complement deposition [133]

Crude polysaccharides

(BCPs)

Acidic polysaccharide (D3-S1)

Bupleurum chinense DC

CH50 = 0.34 ± 0.02 mg/mL

AP50 = 0.081 ± 0.003 mg/mL

(C1s, C3, C4)(D3-S1)

[134]

BCPs can reduce the deposition of complement C3c in the lungs, improve pathological damage, reduce the wet-to-dry weight ratio, significantly reduce the protein concentration, white blood cell count and lung myeloperoxidase in BALF, and reduce IL-6 and TNF-α in BALF and serum to treat two-hit ALI in Wistar rats [120]. The therapeutic effect on ALI of BCPs may be related to its inhibition of the excessive activation of complement and production of pro-inflammatory mediators [121]

Crude polysaccharides (CHCP)

Houttuynia cordata Thunb

CH50 = 0.092 ± 0.020 mg/mL

AP50 = 0.209 ± 0.036 mg/mL (C3 and C4)

CHCP prevented significant macrophage migration induced by C5a and antagonized increased NO and pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β) caused by LPS

CHCP inhibits inappropriate activation of the complement system and may have therapeutic implications for inflammatory diseases. CHCP significantly alleviated ALI induced by LPS. The infiltration of inflammatory cells, the expression of TLR4 and complement deposition were significantly decreased by treatment [118]. CHCP has no interference with the coagulation system [119]

Polysaccharides (JPWP)

Acidic homogeneous polysaccharide isolated from JPWP (JPWP-PS)

Acidic polysaccharide (YB-PS4)

Water-soluble acidic polysaccharide (XB-PS3)

Juniperus pingii var. wilsonii

CH50 = 68 ± 3 μg/mL

AP50 = 93 ± 7 μg/mL (JPWP)

CH50 = 0.073 ± 0.009 mg/mL

(JPWP-PS) [117]

CH50 = 94.23 ± 8.9 μg/mL, AP50 = 194.76 ± 9.2 μg/mL

(C1q, C2, C3, C4 and C5)

(YB-PS4) [135]

CH50 = 117.23 ± 18.74 μg/mL

(C3, C4, C5 and C9)

(XB-PS3)

JPWP significantly attenuated ALI induced by H1N1 influenza virus in vivo through reducing the inflammatory responses, alleviating oxidative stress and inhibiting the activation of complement [136]

Flavonoids-enriched extract

(FESR)

Scutellaria baicalensis Georgi

FESR show no anti-complementary activity in vitro

FESR has great potential in treating H1N1 influenza virus-induced ALI, and the mechanism may be closely related to its antiviral, anti-inflammatory and anti-complement properties. Oral administration of FESR effectively protected infected mice, by increasing survival rate, decreasing lung index, and improving lung morphology. FESR modulated the inflammatory responses in lung tissues (TNF-α, IL-6 and MCP-1↓, IFN-γ and IL-10↑). FESR obviously reduced complement deposition and decreased complement activation product level in the lung [122]

Two new ent-labdane diterpenoids and sixteen known congeners

Andrographis paniculata (Burm.f.) Nees

CH50 and AP50 values of 23.1–638.3 μg/mL and 54.2–603.9 μg/mL, respectively

Andrographis paniculata (Burm.f.) Nees can treat various inflammatory diseases, including ALI [137], common cold and upper respiratory tract infections [138]. The ent-labdane diterpenoids obtained from it have anti-inflammatory, anti-flu and anti-cancer effects [139]

Shen-Fu Injection (SFI)

Panax ginseng C. A.Mey. and Aconitum carmichaelii Debeaux

 

SFI can significantly alleviate immune dysfunction after resuscitation by regulating complement expression and cytokine levels (reduce IL-6, IL-8 and TNF-α; increase IL-4 and IL-10) [123]

  1. CH50 and AP50 stand for 50% hemolytic inhibition concentration through the classical and alternative pathway, respectively. LPS: lipopolysaccharide; BALF: bronchoalveolar lavage fluid; ALI: acute lung injury