Synergistic behaviour of Salvia and Notoginseng species in vascular diseases

As the mainstay and principal form of traditional Chinese medicine (TCM), Chinese herbal medicine (CHM) has been the subject of growing interest and popular use worldwide. However, its unique philosophy, diagnosis and prescription are completely different from Western Medicine (WM), which has brought great challenges for the quality standardisation, safety control, and efficacy evaluation confronting its development in a modernised scientific manner. This PhD project aims to address challenges that revolve around the efficacy research of CHM. Based on CHM theory, the key mechanism of the efficacy of CHM is the synergistic interactions among multiple herbal ingredients in a formula to reach an optimised therapeutic effect, multi-target mode of actions and reduced potential side effects. Several rigorous analytical methods such as combination index (CI), isobolographic analysis and systems biology are designed for the quantitative evaluations of synergistic effects in pharmaceutical combination therapy, and have also been utilised for the study of CHM. Among them, CI and isobologram models are applied for studying the interactions of a small number of active components or herbal extracts on the same target or receptor in which their chemical and pharmacological properties are well defined. A systems biology model may also be used to analyse multi-component, multi-target actions in combinational therapy. However, following a systematic review, it is apparent that the current literature on synergistic study of CHM is still at an early stage. Based on previous studies, we hypothesised that a platform to systematically analyse synergistic interactions of herbal compounds can be established by modern bioassays and scientific models (e.g., CI and isobologram approaches). Herb-pairs are the basic unit for the Chinese herbal formulae. Salvia Miltiorrhiza Radix et Rhizoma and Notoginseng Radix et Rhizome (known as Danshen [DS] and Sanqi [SQ] in TCM) has been one of the most frequently prescribed herb pairs in TCM clinics for cardiovascular disease management for over 30 years in Asian countries. However, very limited mechanistic studies on the combinational benefits on the complex pathological mechanisms of vascular diseases are available, despite the fact that the bioactivities for a single extract have been well studied. Therefore, the DS-SQ herb-pair was selected as a case study to address the issue of synergistic activities in CHM

Integrative Western and Chinese Medicine on Coronary Heart Disease: Where Is the Orientation?

Coronary heart disease (CHD) is the leading cause of death. As the main treatment of CHD, modern medicine has improved dramatically in recent years. Although researches of TCM and integrative medicine on CHD are witnessed encouraging progress in many respects, the role TCM playing in the prevention and treatment of CHD has been unprecedentedly challenged under such circumstance of the very fast development of modern medicine. In order to share mutual complementary advantages of TCM and western medicine, this review summarizes the relatively prominent researches of TCM and integrative medicine on CHD in recent years, and illuminates the issue of the orientation of the further research of integrative medicine on CHD, including (1) original innovation of TCM etiology and pathogenesis, (2) combination of disease and TCM syndrome, (3) biological basis of TCM syndrome of CHD, (4) clinical design and quality control of integrative medicine research, (5) herb-drug interaction, (6) difficulties and hot issues of modern medicine

Chinese herbal medicine for diabetic kidney disease: historical perspective, clinical evidence and new therapeutic development

Diabetic kidney disease (DKD) is the foremost microvascular complication of diabetes mellitus, which is characterised as persistent albuminuria and progressive loss of kidney function induced by diabetes. The health burden of DKD is substantial and continues to grow in parallel with the escalating prevalence of diabetes. Despite current pharmacotherapies including hypoglycaemic agents, hypotensive drugs and reninangiotensin system (RAS) inhibitors, substantial residual risk of DKD initiation and progression remains. Considering the increasing prevalence of DKD, novel renal protective therapeutics are in great need. Chinese herbal medicine (CHM) has been used since antiquity in some countries and regions, and is still being used to treat kidney diseases in combination with contemporary medicine. Guided by traditional knowledge and contemporary practice of herbal application, existing and potentially novel therapeutics for DKD may be evaluated and further developed from CHM. To-date, the development of therapeutics from CHM has been impeded by general lack of clinical evidence, complex chemical profiles and unclear mechanisms of action. Moreover, the conventional drug application of the “one target, one drug” approach has been a limitation when it comes to complex and multi-factorial clinical presentations such as DKD. CHM is a complex intervention that commonly involves a number of herbal ingredients clinically for treating individual patients with DKD. Objectives Guided by a “whole evidence” framework, the aims of this research are to: - Evaluate the classical literature evidence of CHM as a treatment for DKD - Evaluate the clinical trial evidence of CHM as adjunctive therapy for DKD - Explore and propose the bioactive compounds and pharmacological mechanisms of promising CHM for DKD Review of classical literature A search of the classical Chinese medicine literature was conducted in the Zhong Hua Yi Dian (ZHYD, 5th Edition, 2014). A total of 278 DKD-relevant classical citations with treatment information were identified and analysed. These citations were derived from 68 classical Chinese medicine books spanning from AD 583 to AD 1895. Based on the rating results, there were 23 citations that were most likely DKD. Ba wei wan, Liu wei di huang wan and Hui xiang san were the most frequently cited formulae for DKD. The herbs frequently used were huang qi (Astragalus membranaceus (Fisch.) Bge. var. mongholicus (Bge.) Hsiao), ren shen (Panax ginseng C. A. Mey.), wu wei zi (Schisandra chinensis (Turcz.) Baill.), tian hua fen (Trichosanthes kirilowii Maxim.) and huang lian (Coptis chinensis Franch.). It was found that citations with positive turbid urine symptoms used huang qi more often than other high-frequency herbs. Systematic reviews of randomised controlled trials The Cochrane handbook of systematic reviews of interventions (version 5.1.0) guided the methods of the systematic reviews. The first systematic review included 20 randomised controlled trials (RCT) with 2719 DKD patients comparing CHM with placebo. Meta-analysis suggested that CHM reduced greater albuminuria than placebo, regardless of whether RAS inhibitors were concurrently administered. When CHM was used as an adjunct to RAS inhibitors, estimated glomerular filtration rate (eGFR) was improved in the CHM group compared with the placebo group. The adverse events (AE) rates were low and similar between CHM and placebo groups. Huang qi was used most frequently among included RCTs. Accroding to the results of the first systematic review and classical literature review, the herb huang qi was selected as a subject for further study. The second systematic review included 66 RCTs employing sole huang qi preparations with 4785 DKD participants. Overall, the included studies have substantial risk of bias due to methodological shortfalls. The meta-analysis showed that additional use of huang qi injection reduced albuminuria, proteinuria and serum creatinine concentration compared to conventional therapy alone. An anti-albuminuria effect was also reported in the oral huang qi preparation group. The safety of huang qi prepareations was uncertain because AEs were only reported in one third of included studies. More detailed safety evaluation particularly for huang qi injections are needed due to severe allergic reactions after injections have been observed. Network pharmacology study Network pharmacology is a novel drug discovery approach that uses data from highthroughput experiments, omics studies and other biological research and integrates and analyses them as a whole. It was applied to visualise and predict the complex relationships underlying the numerous DKD targets and multiple herbal compounds. The herb huang qi was selected for the network pharmacology study based on the results reported above. Searching retrieved 103 distinct human targets related to DKD. Thirty-eight (38) bioactive compounds from huang qi were identified, with a corresponding 327 targets. The huang qi–DKD PPI network contained 2269 shared targets, and 127 of these were considered to play central communication roles. These key targets were enriched in 174 biological pathways and the most significant pathways were integrin-linked kinase (ILK) signalling, tumour necrosis factor-related apoptosisinducing ligand (TRAIL) signalling, transforming growth factor beta (TGFβ)/Smad2/3 signalling, vascular endothelial growth factor (VEGF) and VEGF receptor (VEGFR) signalling network and glypican/glypican-1 pathway. Further analysis of the herbal compounds-key targets-pathways network revealed that quercetin, calycosin, formononetin, kaempferol, isorhamnetin, betulinic acid, gamma-sitosterol, (24S)-24-Propylcholesta-5-ene-3beta-ol and bifendate were directly associated with 21 key targets enriched in the top 10 pathways. Conclusion By employing a whole evidence strategy, this research systematically evaluated the current best available evidence about CHM as adjunctive therapy for DKD, from both historical and contemporary perspectives. Classical literature evidence indicated that huang qi was commonly used in DKD-like disorders, particularly for those presenting with turbid urine (cloudy or foamy urine). With moderate to low quality evidence from RCTs, CHM may have beneficial effects on renal function and albuminuria beyond those reported by conventional treatment alone in adults with DKD. Moreover, adjunctive use of sole huang qi preparations with RAS inhibitors appeared to lowering albuminuria/proteinuria, as well as reducing serum creatinine concentration in the short term. The pharmacological actions of huang qi could be mediated by ILK signalling, TGF-β/Smad signalling, NF-κB pathway and glypican/glypican-1 pathway. Eight compounds with direct potential to regulate key targets are provided as new therapeutic development candidates for DKD. Hence, further research is warranted to determine their clinical benefit

Emerging Applications of Metabolomics in Traditional Chinese Medicine Treating Hypertension: Biomarkers, Pathways and More

Hypertension is a prevalent, complex, and polygenic cardiovascular disease, which is associated with increased mortality and morbidity. Across the world, traditional Chinese medicine (TCM) constituted by herbal medicine and non-pharmacological therapies is used to assist blood pressure management. Though widely accepted in daily practice, its mechanism remains largely unknown. Recent years saw a number of studies utilizing metabolomics technologies to elucidate the biological foundation of the antihypertensive effect of TCM. Metabolomics is a relatively “young” omics approach that has gained enormous attention recently in cardiovascular drug discovery and pharmacology studies of natural products. In this review, we described the use of metabolomics in deciphering TCM diagnostic codes for hypertension and in revealing molecular events that drive the antihypertensive effect. By corroborating the diagnostic rules, there's accumulating evidence showing that metabolic profile could be the signature of different syndromes/patterns of hypertension, which offers new perspectives for disease diagnosis and efficacy optimization. Moreover, TCM treatment significantly altered the metabolic perturbations associated with hypertension, which could be a crucial mechanism of the therapeutic effect of TCM. Not only significantly rebalances the dynamics of metabolic flux, TCM but also elicits metabolic network reorganization through restoring the functions of key metabolites, and metabolic pathways. The role of TCM in regulating metabolic perturbations will be informative to researchers seeking new leads for drug discovery. This review further envisioned the promises of employing metabolomics to explore network pharmacology, host-gut microbiota interactions and metabolic reprogramming in TCM, and possible herb-drug interactions in this field in future

Traditional Chinese Herbal Medicine – East Meets West in Validation and Therapeutic Application

Author name used in this publication: Sonny H. M. Tse2011-2012 > Academic research: refereed > Chapter in an edited book (author)published_fina

Network Pharmacology-Based Approach to Investigate the Analgesic Efficacy and Molecular Targets of Xuangui Dropping Pill for Treating Primary Dysmenorrhea

published_or_final_versio

Synergistic Effects of Chinese Herbal Medicine: A Comprehensive Review of Methodology and Current Research

Traditional Chinese medicine (TCM) is an important part of primary health care in Asian countries that has utilized complex herbal formulations (consisting 2 or more medicinal herbs) for treating diseases over thousands of years. There seems to be a general assumption that the synergistic therapeutic effects of Chinese herbal medicine (CHM) derive from the complex interactions between the multiple bioactive components within the herbs and/or herbal formulations. However, evidence to support these synergistic effects remains weak and controversial due to several reasons, including the very complex nature of CHM, misconceptions about synergy and methodological challenges to study design. In this review, we clarify the definition of synergy, identify common errors in synergy research and describe current methodological approaches to test for synergistic interaction. We discuss the strengths and weaknesses of these models in the context of CHM and summarize the current status of synergy research in CHM. Despite the availability of some scientific data to support the synergistic effects of multi-herbal and/or herb-drug combinations, the level of evidence remains low, and the clinical relevancy of most of these findings is undetermined. There remain significant challenges in the development of suitable methods for synergistic studies of complex herbal combinations

Investigating the Use and Identity of Traditional Herbal Remedies Amongst South Asian Communities Using Surveys and Bimolecular Techniques.

Herbal medicines (HMs) have been used to supplement, maintain, and treat health conditions, and have inspired the development of many Western pharmaceuticals. Migrant South Asian (SA) communities in the UK have brought with them their own traditional forms of medicine, yet little is known about their current use of HMs in the UK. Consuming HMs alongside conventional Western medicines could affect pharmacological treatment and lead to herb-drug interactions; hence, healthcare professionals (HCPs) should be aware of their patients’ use of HMs. The import of HMs to the UK raises concerns over the quality, safety and regulation of HMs. Deoxyribonucleic acid (DNA) barcoding can be used to discriminate between different species, and identify contaminants and adulterants, thus can be used for the authentication of HMs. The South Asian Traditional Medicines (SATMED) questionnaire explored the knowledge and use of HMs by diasporic SA communities in the UK. It uncovered a vast range of HMs which were used by participants, where ingredients were sourced from, the concurrent use of herbal and Western medicines, and how minor ailments were treated. An online survey designed to investigate UK based practitioners’ views of HMs revealed that HCPs claimed to lack sufficient knowledge of HMs. HCPs said they needed more training on HMs to help them make better informed decisions. Tulsi (Ocimum tenuiflorum L.) was identified as a culturally and commercially valuable plant, which was used for molecular analysis. A variety of tulsi samples were collected for authentication: community samples from SA families in the UK, commercial samples, and referenced specimens. Both ITS and trnH-psbA regions were successfully used to distinguish between several Ocimum species, and identify a potential species substitution. This research represents the first time that DNA based methods have been used to authenticate medicinal plants species used by migrant SA communities living in the UK. The results of this multi-disciplinary study provide a unique contribution to the evolving discipline of ethnopharmacology

Evolution of the adaptogenic concept from traditional use to medical systems: Pharmacology of stress- and aging-related diseases

Adaptogens comprise a category of herbal medicinal and nutritional products promoting adaptability, resilience, and survival of living organisms in stress. The aim of this review was to summarize the growing knowledge about common adaptogenic plants used in various traditional medical systems (TMS) and conventional medicine and to provide a modern rationale for their use in the treatment of stress-induced and aging-related disorders. Adaptogens have pharmacologically pleiotropic effects on the neuroendocrine-immune system, which explain their traditional use for the treatment of a wide range of conditions. They exhibit a biphasic dose-effect response: at low doses they function as mild stress-mimetics, which activate the adaptive stress-response signaling pathways to cope with severe stress. That is in line with their traditional use for preventing premature aging and to maintain good health and vitality. However, the potential of adaptogens remains poorly explored. Treatment of stress and aging-related diseases require novel approaches. Some combinations of adaptogenic plants provide unique effects due to their synergistic interactions in organisms not obtainable by any ingredient independently. Further progress in this field needs to focus on discovering new combinations of adaptogens based on traditional medical concepts. Robust and rigorous approaches including network pharmacology and systems pharmacology could help in analyzing potential synergistic effects and, more broadly, future uses of adaptogens. In conclusion, the evolution of the adaptogenic concept has led back to basics of TMS and a new level of understanding of holistic approach. It provides a rationale for their use in stress-induced and aging-related diseases

Review Article Trends in the Treatment of Hypertension from the Perspective of Traditional Chinese Medicine

Hypertension is a major public-health issue. Much consensus has been reached in the treatment, and considerable progress has been made in the field of antihypertensive drugs. However, the standard-reaching rate of blood pressure is far from satisfaction. Considering these data and the seriousness of the effects of hypertension on the individual and society as a whole, both economically and socially, physicians must look for more effective and alternative ways to achieve the target blood pressure. Could treatment of hypertension be improved by insights from traditional Chinese medicine? As one of the most important parts in complementary and alternative therapies, TCM is regularly advocated for lowering elevated blood pressure. Due to the different understanding of the pathogenesis of hypertension between ancient and modern times, new understanding and treatment of hypertension need to be reexplored. Aiming to improve the efficacy of Chinese herbal medicine in treating hypertension, the basis of treatment is explored through systematically analyzing the literature available in both English and Chinese search engines. This paper systematically reviews the trends in emerging therapeutic strategies for hypertension from the perspective of traditional Chinese medicine