Gaps and feasibility of fixed-dose combination strategy in the development of modern Chinese medicine

isTraditional Chinese medicine(TCM)is a highly complex chemical substance system,which not only reflected in the complexity of the chemical components and their interrelationships,but also in the intricacy of the prescription’s connection with the human body.Component compatibility strategy has been proposed for developing modern TCM since 2005 and established comprehensive relevant technologies and research approaches.Moreover,to meet the safety and efficacy of current pharmaceuticals,research on fixed-dose combination drugs is directed by modern scientific theories,conforms to TCM compatibility principles and clarifies material basis and pharmacological mechanisms and component-effect correlations.This review summarized gaps and feasibility of fixed-dose combination strategy in the development of modern TCM research and assessed their advantages and disadvantages in light of contemporary drug combination research practices.

Effect of salvianolic acid A and C compatibility on inflammatory cytokines in rats with unilateral ureteral obstruction

OBJECTIVE:To investigate the effect of salvianolic acid A and C component molecules,which are involved in drug compatibility,on inflammatory cytokine expression that affects human chemokine ligand 5(CCL5) and chemokine ligand 10(CXCL10)levels in rats with unilateral ureteral obstruction(UUO).METHODS:Fifty Sprague Dawley rats were randomly divided into five groups:normal,model,salvianolic acid A,salvianolic acid C and salvianolic acid A and C groups.The normal group was used as the control,and the other groups of rats had a UUO model established.The control group had free access to food and water,and the other groups received the corresponding drugs for 2 weeks.After the last administration,urine β_2-microglobulin(β_2-MG) and N-acetyl-β-D-glucosaminidase(NAG) levels were analyzed.After 24 h,all rats were sacrificed and the serum was analyzed for creatinine(Cr) and blood urea nitrogen(BUN) levels.Rat kidneys were removed,and CCL5 and CXCL10 inflammatory cytokine mRNA expression was measured using real-time fluorescent quantitative reverse transcription-polymerase chain reaction(RT-PCR).Kidney fibrosis was observed using hematoxylin-eosin(HE)staining and Masson trichrome staining.RESULTS:In the salvianolic acid A and salvianolic acid C treatment groups,serum Cr and urine NAG levels were significantly lower than in the model group(both P < 0.05).In all treatment groups,urine pYMG levels were significantly lower than in the model group(all P < 0.05).Compared with model group,the pathological changes and collagen deposition improved to varying degrees(both P <0.05).CCL5 and CXCL10 mRNA expression decreased to different degrees compared with the model group(both P < 0.05).CONCLUSION:Salvianolic acid A and C are component molecules of drug compatibility,and they may protect renal function and improve tubular function and renal pathology to a certain degree in UUO.This improvement may be related to a reduction in inflammatory cytokines CCL5 and CXCL10 secretion in the UUO rat kidney.

Relaxant Effect of Bioactive Component Compatibility of San-ao Decoction on In vitro Guinea Pig Airway Smooth Muscle:A Dose-Response Relationship Study

Background:Component compatibility is important to the modernization of traditional Chinese medicine.Studies have shown that San-ao decoction(SAD)can treat respiratory diseases by relaxing airway smooth muscle(ASM)and reducing airway hyper-responsiveness.However,whether its bioactive components and compatibility also present with similar relaxant effects remains unknown.This study aims to explore the potential relaxant property,dose-response relationship,and underlying mechanisms of the bioactive component compatibility in SAD.Methods:Network pharmacology was primarily used to identify the bioactive components of SAD and uncover its underlying mechanisms.ASM tension force measuring technique was utilized to verify the relaxant and dose-response effects on in vitro guinea pig ASM.Results:We postulated pseudoephedrine hydrochloride(PH),amygdalin(AM),and diammonium glycyrrhizate(DG)to be the bioactive components of SAD,which could effectively relax ASM in a dose-dependent manner on both acetylcholine-induced and spontaneous contraction.Both PH and AM could lead to DG dose–response curve shift.The regression equation of these three bioactive components was Y=-2.048×X_(1)+0.411×X_(2)+14.052×X_(3)(X_(1),X_(2),X_(3)representing PH,AM,and DG,respectively).The underlying mechanisms of these components might be associated with the regulation of smooth muscle contraction.Conclusions:PH,AM,and DG are the bioactive components of SAD,which can relax ASM in a dose–response manner and exert a synergistic effect.Clinically,compatibility of these three bioactive components may serve as a new complementary and alternative treatment for respiratory diseases.

Protective effects of Yindanxinnaotong capsule in a rat model of myocardial ischemia/reperfusion injury

OBJECTIVE: To investigate the effects of Yindanxinnaotong capsule(YDXNTC) and main components compatibility and ratios on myocardium against ischemia/reperfusion injury and the effect's underlying mechanism.METHODS: Myocardial ischemia/reperfusion injury(MIRI) was induced by ischemia for 30 min and reperfusion for 30 min. Electrocardiogram data and coronary flow were recorded, and superoxide dismutase(SOD), malondialdehyde(MDA), lactate dehydrogenase, creatine kinase-MB, cardiac troponin T and I(cT nT, cT n I) and interleukin-1β, interleukin-8,interleukin-18(IL-1β, IL-8, IL-18) in myocardium were measured. Hypoxia/reoxygenation and hydrogen peroxide(H2O2) injury were induced by hypoxia for 3 h/reoxygenation for 2 h, and 100 μM H2O2 for 1 h, respectively, in vitro rat myocardial cells(H9c2). Cell viability, SOD, MDA, cT nT and inflamma-tory factors(IL-1β, IL-8 and IL-18) were determined,and Toll-like receptor 4(TLR-4) expression was measured by western blotting.RESULTS: In the isolated heart experiment, elevated heart function, coronary flow and SOD levels,and decreased MDA levels and inflammatory factors were noted in the YDXNTC, main components and main components compatibility groups. Ventricular tachycardia/ventricular fibrillation occurrence decreased in the ginkgo biloba extract(GBE),and GBE and salvia miltiorrhiza ethanol extract compatibility(SM-E, GSEC) groups. Lactic dehydrogenase levels decreased in the YDXNTC and aqueous extract of salvia miltiorrhiza(SM-H) groups. Creatine kinase-MB decreased with GBE, SM-E, SM-H and GSEC treatment, and cT n I and cT nT levels decreased with GSEC. In the in vitro cell study,YDXNTC and main components ratios improved cell viability and SOD levels, and suppressed MDA,cT nT and inflammatory factors. TLR-4 expression was down-regulated.CONCLUSION: YDXNTC and main components compatibility showed protective effects on MIRI in this rat model and in vitro study. Regulating the Toll-like receptor signaling pathway may affect the mechanism.