Chinese herbal medicine-derived compounds for cancer therapy: A focus on hepatocellular carcinoma

Ethnopharmacological relevance

Hepatocellular carcinoma (HCC) as the major histological subtype of primary liver cancer remains one of the most common malignancies worldwide. Due to the complicated molecular pathogenesis of HCC, the option for effective systemic treatment is quite limited. There exists a critical need to explore and evaluate possible alternative strategies for effective control of HCC. With a long history of clinical use, Chinese herbal medicine (CHM) is emerging as a noticeable choice for its multi-level, multi-target and coordinated intervention effects against HCC. With the aids of phytochemistry and molecular biological approaches, in the past decades many CHM-derived compounds have been carefully studied through both preclinical and clinical researches and have shown great potential in novel anti-HCC natural product development. The present review aimed at providing the most recent developments on anti-HCC compounds derived from CHM, especially their underlying pharmacological mechanisms.

Materials and methods

A systematic search of anti-HCC compounds from CHM was carried out focusing on literatures published both in English (PubMed, Scopus, Web of Science and Medline) and in Chinese academic databases (Wanfang and CNKI database).

Results

In this review, we tried to give a timely and comprehensive update about the anti-HCC effects and targets of several representative CHM-derived compounds, namely curcumin, resveratrol, silibinin, berberine, quercetin, tanshinone II-A and celastrol. Their mechanisms of anti-HCC behaviors, potential side effects or toxicity and future research directions were discussed.

Conclusion

Herbal compounds derived from CHM are of much significance in devising new drugs and providing unique ideas for the war against HCC. We propose that these breakthrough findings may have important implications for targeted-HCC therapy and modernization of CHM.     

Chinese herbal medicine for COVID-19: Current evidence with systematic review and meta-analysis

BackgroundThere is currently no drug or therapy that cures COVID-19, a highly contagious and life-threatening disease.ObjectiveThis systematic review and meta-analysis summarized contemporary studies that report the use of Chinese herbal medicine (CHM) to treat COVID-19.Search strategySix electronic databases (PubMed/MEDLINE, Cochrane Library, ScienceDirect, Google Scholar, Wanfang Data and China National Knowledge Infrastructure) were searched from their beginning to May 15, 2020 with the following search terms: traditional Chinese medicine, Chinese medicine, Chinese herbal medicine, COVID-19, new coronavirus pneumonia, SARS-CoV-2, and randomized controlled trial.Inclusion criteriaRandomized controlled trials (RCTs) from peer-reviewed journals and non-reviewed publications were included. Further, included RCTs had a control group that was given standard care (SC; such as conventional Western medicine treatments or routine medical care), and a treatment group that was given SC plus CHM.Data extraction and analysisTwo evaluators screened and collected literature independently; information on participants, study design, interventions, follow-up and adverse events were extracted, and risk of bias was assessed. The primary outcomes included scores that represented changes in symptoms and signs over the course of treatment. Secondary outcomes included the level of inflammatory markers, improvement of pneumonia confirmed by computed tomography (CT), and adverse events. Dichotomous data were expressed as risk ratio or hazard ratio with 95% confidence interval (CI); where time-to-event analysis was used, outcomes were expressed as odds ratio with 95% CI. Continuous data were expressed as difference in means (MD) with 95% CI, and standardized mean difference (SMD) was used when different outcome scales were pooled.ResultsSeven original studies, comprising a total of 732 adults, were included in this meta-analysis. Compared to SC alone, CHM plus SC had a superior effect on the change of symptom and sign score (−1.30 by SMD, 95% CI [−2.43, −0.16]; 3 studies; n = 261, P = 0.03), on inflammatory marker C-reactive protein (CRP, mg/L; −11.82 by MD, 95% CI [−17.95, −5.69]; 5 studies; n = 325, P = 0.0002), on number of patients with improved lung CT scans (1.34 by risk ratio, 95% CI [1.19, 1.51]; 4 studies; n = 489, P < 0.00001). No significant adverse events were recorded in the included RCTs.ConclusionCurrent evidence shows that CHM, as an adjunct treatment with standard care, helps to improve treatment outcomes in COVID-19 cases.     

Salvia miltiorrhiza: An ancient Chinese herbal medicine as a source for anti-osteoporotic drugs

Ethnopharmacological relevance

Red sage (Salvia miltiorrhiza Bunge), also known as Danshen in Chinese, has been used historically and is currently exploited in combination with other herbs to treat skeletal diseases in traditional Chinese medicine (TCM). With the advance of modern analytical technology, a multitude of bone-targeting, pharmaceutically active, compounds has been isolated and characterized from various sources of TCM including those produced in Salvia miltiorrhiza root. The aim of the review is to provide a comprehensive overview about the historical TCM interpretation of the action of Salvia miltiorrhiza in osteoporosis, its use clinical trials, its main phytochemical constituents, and its action on bone-resorptive and bone formation-stimulating mechanisms in in vitro and in vivo studies.

Materials and methods

Literature sources used were Pubmed, CNKI.net, Cqvip.com, PubChem, and the Web of Science. For the inquiry, keywords such as Salvia, danshen, osteoporosis, bone, osteoclast and osteoblast were used in various combinations. About 130 research papers and reviews were consulted.

Results

In TCM, the anti-osteopororotic effect of Salvia miltiorrhiza is ascribed to its action on liver and blood stasis as main therapeutic targets defining osteoporosis. 36 clinical trials were identified which used Salvia miltiorrhiza in combination with other herbs and components to treat post-menopausal, senile, and secondary osteoporosis. On average the trials were characterized by high efficacy (>80%) and low toxicity problems. However, various limitations such as small patient samples, short treatment duration, frequent lack of detailed numerical data, and no clear endpoints must be taken into consideration. To date, more than 100 individual compounds have been isolated from this plant and tested in various animal models and biochemical assays. Compounds display anti-resorptive and bone formation-stimulating features targeting different pathways in the bone remodeling cycle. Pathways affected include the activation of osteoblasts, the modulation of osteoclastogenesis, and the inhibition of collagen degradation by cathepsin K.

Conclusions

The inclusion of Salvia miltiorrhiza in more than 30% of all herbal clinical trials successfully targeting osteoporosis has stimulated significant interest in the identification and characterization of individual constituents of this herb. The review highlights the anti-osteoporotic potential of Salvia miltiorrhiza in clinical applications and the potential of the herb to provide potent compounds targeting specific pathways in bone resorption and bone formation.     

靶向表皮生长因子受体治疗结直肠癌的耐药机制及中药研究进展

综述靶向表皮生长因子受体(EGFR)治疗结直肠癌的耐药机制和中药研究进展。EGFR信号通路的分子改变和代偿性信号通路的异常激活是抗-EGFR治疗耐药发生的主要机制。中药多靶点的作用特点,使其在逆转肿瘤耐药方面具有明显优势。多种中药及其有效成分不仅具有直接抗肿瘤作用,与靶向药物联合使用还可以增强抗肿瘤西药敏感性,并克服肿瘤耐药,值得进一步深入研究。     

Prospective randomized controlled study of a Chinese herbal medicine compound Tangzu Yuyang Ointment for chronic diabetic foot ulcers: a preliminary report

Aim of the study

The purpose of this study was to evaluate the efficacy and safety of a topical Chinese herbal medicine (CHM) compound Tangzu Yuyang Ointment (TYO) for treatment of chronic diabetic foot ulcers.

Materials and methods

This multi-center, prospective, randomized, controlled and add-on clinical trial was conducted at seven centers in the China mainland. Fifty-seven patients with chronic diabetic foot ulcers of Wagner's ulcer grade 1-3 were enrolled in this study. Patients who were randomly assigned to the control group (n = 28) received standard wound therapy (SWT), whereas those randomized to the treatment group (n = 28) received SWT plus topical TYO. Only 48 patients who finished 24 weeks of observations were entered for data analysis.

Results

The TYO and SWT groups were comparable for baseline characteristics. Ulcer improvement was 79.2% in the TYO group and 41.7% in the SWT group (P = 0.017) at 12 weeks, and 91.7% vs. 62.5% (P = 0.036) at 24 weeks. The number of ulcers that were completely healed at 4, 12 and 24 weeks was similar in both groups, as were the numbers of adverse events. Healing time was 96 ± 56 days (n = 19) in the TYO group and 75 ± 53 days (n = 14) in the SWT group (P = 0.271).

Conclusion

TYO plus SWT is more effective than SWT in the management of chronic diabetic foot ulcers and has few side-effects.     

Comparable effects of Jiedu Granule,a compound Chinese herbal medicine,and sorafenib for advanced hepatocellular carcinoma: A prospective multicenter cohort study

ObjectiveSorafenib has been extensively used for the treatment of advanced hepatocellular carcinoma (HCC), and Chinese herbal medicine has also been used to manage advanced HCC. The present work evaluates the effectiveness and safety of Jiedu (JD) Granule, a compound of traditional Chinese herbal medicine, side-by-side with sorafenib for the treatment of advance HCC.MethodsPatients with advanced HCC receiving treatment with JD Granule or sorafenib were enrolled from December 2014 to March 2018. The primary endpoint was overall survival (OS). The secondary endpoints were progression-free survival (PFS) and safety. Propensity score matching (PSM) analysis was used to control for possible selection bias from the study group allocation process.ResultsOf the 325 patients included, 161 received JD Granule and 164 received sorafenib. No significant differences were found in OS or PFS among patients receiving JD Granule compared to sorafenib (P > 0.05). Median OS of the two study groups was 6.83 months (95% confidence interval [CI]: 5.83–9.47) in the group receiving JD Granule and 8 months (95% CI: 6.67–9.80) in the group receiving sorafenib, with half-, 1- and 2-year survival rates of 53.6%, 31.2% and 13.2% vs 60.1%, 35.5% and 14.2%, respectively. Even after PSM, the median survival time did not differ between the JD Granule group (9.03 months; 95% CI: 6.37–14.2) and the sorafenib group (7.93 months; 95% CI: 6.5–9.97), with comparable half-, 1- and 2-year survival rates. The most common adverse events (AEs) were diarrhea (13.7%) and fatigue (5.6%) in the JD Granule group, and hand-foot skin reaction (46.3%) and diarrhea (36.6%) in the sorafenib group. The JD Granule was more cost-effective than sorafenib treatment for advanced HCC.ConclusionCompared to sorafenib, JD Granule was more cost-effective and caused fewer AEs for the treatment of Chinese patients with advanced HCC.     

Compatibility art of traditional Chinese medicine: From the perspective of herb pairs

Ethnopharmacological relevance

Over the past decades, research of traditional Chinese medicine (TCM) mainly focused on developing potential candidates from Chinese medicinal herbs, while the wisdom of applying these traditional herbs has not been paid as much attention as it deserves. As is well-known, multi-herb therapy is one of the most important characteristics of TCM, but the modernization drive of this conventional wisdom has faced many obstacles due to its unimaginable complexity. Herb pairs, the most fundamental and the simplest form of multi-herb formulae, are a centralized representative of Chinese herbal compatibility. In light of their simplicity and the basic characteristics of complex formulae, herb pairs are of great importance in the studies of herb compatibility.

Materials and methods

A systematic search of herb pair related research was carried out using multiple online literature databases, books and monographs published in the past 20 years.

Results

A comprehensive introduction to the compatibility of TCM, the position of herb pairs in TCM and the progresses of several famous herb pairs were provided in this review. Furthermore, the clinical study and the future research trends of herb pairs were also discussed.

Conclusions

Herb pairs have played, and may continue to play a key role in full investigation of general herb compatibility for their indispensable position in TCM. Much more research is needed for the standardization, safety evaluation, and mechanism exploration of herb pairs.     

Traditional Chinese medicinal herbs combined with epidermal growth factor receptor tyrosine kinase inhibitor for advanced non-small cell lung cancer: a systematic review and meta-analysis

BACKGROUND: Epidermal growth factor receptor tyrosine kinase inhibitor(EGFR-TKI) targeted treatment has been a standard therapy for advanced non-small cell lung cancer(NSCLC), but it is not tolerated well by all patients. In China, some studies have reported that traditional Chinese medicinal herbs(TCMHs) may increase effi cacy and reduce toxicity when combined with EGFR-TKI, but outside of China few studies of this kind have been attempted. OBJECTIVE: This study is intended to systematically review the existing clinical evidence on TCMHs combined with EGFR-TKI for treatment of advanced NSCLC. SEARCH STRATEGY: PubMed, the Cochrane Library, the Excerpta Medica Database(EMBASE), the China BioMedical Literature(CBM), and the China National Knowledge Infrastructure(CNKI) and web site of the American Society of Clinical Oncology(ASCO), the European Society for Medical Oncology(ESMO), the World Conference of Lung Cancer(WCLC) were searched; the search included all documents published in English or Chinese before October 2013. INCLUSION CRITERIA: We selected randomized controlled trials based on specifi c criteria, the most important of which was that a TCMH plus EGFR-TKI treatment group was compared with an EGFR-TKI control group in patients with advanced NSCLC. DATA EXTRACTION AND ANALYSIS: The modifi ed Jadad scale was used to assess the quality of studies. For each included study, patient characteristics, treatment details, therapeutic approach and clinical outcomes were collected on a standardized form. When disagreements on study inclusion or data extracted from a study emerged, the consensus of all coauthors provided the resolution. The clinical outcome metrics consisted of objective response rate(ORR; complete response + partial response divided by the total number of patients), disease control rate(DCR; complete response + partial response + no change divided by the total number of patients), survival rate, improved or stabilized Karnofsky performance status(KPS), and severe toxicity. RevMan 5.0 software was used for data syntheses and analyses. Risk ratio(RR) and 95% confidence interval(CI) were calculated; if the hypothesis of homogeneity was not rejected(P0.1, I250%), the fi xed-effect model was used to calculate the summary RR and the 95% CI. Otherwise, a random-effect model was used.RESULTS: In this review, 19 studies were included based on the selection criteria. Of them, 13studies were of high quality and 6 studies were of low quality, according to the modifi ed Jadad scale. When the TCMH plus EGFR-TKI treatment groups were compared with the EGFR-TKI control groups the meta-analysis demonstrated a statistically signifi cant higher ORR(RR 1.34; 95% CI 1.15 to 1.57; P=0.000 2), DCR(RR 1.18; 95% CI 1.09 to 1.27; P0.000 1), one-year survival rate(RR 1.21; 95% CI 1.01 to 1.44; P=0.04), 2-year survival rate(RR 1.91; 95% CI 1.26 to 2.89; P=0.002) and improved or stable KPS(RR 1.38; 95% CI 1.26 to 1.51; P0.000 01). Severe toxicity for rash was decreased(RR 0.55; 95% CI 0.32 to 0.94; P=0.03), as were nausea and vomiting(RR 0.17; 95% CI 0.04 to 0.72; P=0.02) and diarrhea(RR 0.46; 95% CI 0.24 to 0.89; P=0.02). Sensitivity analysis indicated that fi ndings of the meta-analysis were robust to study quality. In the funnel plot analysis, asymmetry was observed, and publication bias was indicated by Egger's test(P=0.03).CONCLUSION: TCMH intervention can increase effi cacy and reduce toxicity when combined with EGFR-TKI for advanced NSCLC, although this result requires further verifi cation by more well designed studies.     

Chinese herbal medicine for incomplete immune reconstruction in patients with AIDS undergoing antiretroviral treatment: A systematic review of randomized trials

ObjectiveTo evaluate the effectiveness and safety of Chinese herbal medicines (CHMs) for incomplete immune reconstruction in patients with HIV/AIDS.MethodsEight electronic databases were searched for randomized controlled trials (RCTs) on the use of CHM for patients with HIV/AIDS with incomplete immune reconstruction. Outcomes included CD4⁺ cell count, quality of life, and adverse events/effects. The Cochrane Risk of Bias was employed to evaluate the methodological quality of the included RCTs.ResultsWe identified 13 eligible RCTs, with an overall high risk of bias, on 10 different CHMs. There was a significant increase in CD4⁺ cell count after the use of Jianpi Yiqi medicinal paste for 3 months; tripterygium glycosides tablets (TGTs) for 3 months (mean difference [MD] 52.63 cells/μL, 95% confidence interval [CI, 46.98, 58.28]), 6, 9, and 12 months; Wenshen Jianpi granules for 6 months; Shenling Fuzheng capsules for 6 months (MD 49.53 cells/μL, 95% CI [8.45, 90.61]) and 12 months; Aikeqing granules for 9 months (MD 61.51 cells/μL, 95% CI [16.25, 106.77]) and 12 months; Guipi decoction for 12 months; Mianyi No.2 granules (JT) for 12 and 18 months; and Chinese medicine granules for 18 months. The increase in the mean difference of CD4⁺ cell count from 6 to 18 months was larger in Chinese medicine granules and Mianyi No.2 granules (JT). Guipi decoction and Jianpi Qushi decoction improved the Karnofsky score. Four RCTs reported the outcome of adverse events/effects, while four cases of minor adverse effects were reported in the TGTs group.ConclusionJianpi Yiqi medicinal paste, Wenshen Jianpi granules, Shenling Fuzheng capsules, Aikeqing granules, Guipi decoction, and TGTs may be effective in increasing CD4⁺ within 12 months, and Mianyi No.2 granules (JT) and Chinese medicine granules may show long-term effects. High-quality large RCTs on the effectiveness and safety of CHMs are still warranted.     

The use of Chinese herbal products and its influence on tamoxifen induced endometrial cancer risk among female breast cancer patients: A population-based study

Ethnopharmacological relevance

The increased practice of traditional Chinese medicine (TCM) worldwide has raised concerns regarding herb–drug interactions. The purpose of our study was to analyze the use of Chinese herbal products (CHPs) and to estimate the influence of the use of CHP on tamoxifen induced endometrial cancer risk among female breast cancer patients in Taiwan.

Methods

All patients newly diagnosed with invasive breast cancer receiving tamoxifen treatment from January 1, 1998 to December 31, 2008 were selected from the National Health Insurance Research Database. The usage, frequency of service, and CHPs prescribed among the 20,466 tamoxifen-treated female breast cancer patients were analyzed. The logistic regression method was employed to estimate the odds ratios (ORs) for utilization of CHPs. Cox proportional hazard regression was performed to calculate the hazard ratios (HRs) for subsequent endometrial cancer for CHP non-users and CHP users among female breast cancer patients who had undergone tamoxifen treatment.

Results

More than half of the subjects had ever used a CHP. Jia-Wei-Xiao-Yao-San (Augmented Rambling Powder) and Shu-Jing-Huo-Xue-Tang (Channel-Coursing Blood-Quickening Decoction) were the two most commonly used CHPs. The HR for the development of endometrial cancer among CHP users was 0.50-fold (95% CI=0.38–0.64) compared to that of CHP non-users.

Conclusion

More than half of the study subjects had ever used a CHP. Jia-Wei-Xiao-Yao-San was the most commonly used CHP. Among female breast cancer patients who had undergone tamoxifen therapy, CHP consumption decreased the risk of subsequent endometrial cancer. Exploring potential Chinese herb–tamoxifen interactions and integrating both healthcare approaches are beneficial to the overall health outcomes of tamoxifen-treated female breast cancer patients.     

子宫内膜异位症患者中西医结合治疗前后血清血管内皮生长因子及糖类抗原-125的含量变化

目的观察子宫内膜异位症(EMT)患者中西医结合治疗前后血清血管内皮生长因子(VEGF)及糖类抗原-125(CA125)水平的变化及临床意义。方法将30例EMT患者设为治疗组,予中西医结合治疗,检测其血清VEGF及CA125水平。同时选择30例健康体检者作为对照组。结果治疗组Ⅰ～Ⅱ期血清VEGF、CA125含量低于Ⅲ～Ⅳ期(P<0.01)。治疗组子宫内膜分泌期血清VEGF、CA125含量低于增生期(P<0.05)。对照组子宫内膜分泌期血清VEGF、CA125含量与增生期比较差异无统计学意义(P>0.05)。治疗组治疗后血清VEGF、CA125含量低于治疗前(P<0.01),说明中西医结合治疗有效。治疗组治疗后血清VEGF、CA125含量与对照组比较差异无统计学意义(P>0.05)。结论 EMT的发生、发展与血清VEGF及CA125水平密切相关,检测EMT患者血清VEGF、CA125水平对EMT的治疗及预后具有重要的临床价值。     

Chemotherapy in conjunction with traditional Chinese medicine for survival of elderly patients with advanced non-small-cell lung cancer: protocol for a randomized double-blind controlled trial

BACKG ROUND: Traditional Chinese medicine(TCM) is considered an important complementary therapy with beneficial effects for cancer patients.Elderly patients with non-small-cell lung cancer(NSCLC) are a complex patient group with increasing co-morbidity and shrinking physiological reserve, and may derive substantial benefit from the supportive aspects of TCM.Researchers from Shanghai Longhua Hospital found that qi and yin deficiency is a common syndrome in patients with stage III or IV lung cancer.This project was designed to study the combination of single-agent chemotherapy with TCM methods of benefiting qi and yin in elderly patients with advanced NSCLC.METHODS AND DESIGN: This is a double-blind controlled, multi-center, and prospective study with randomly selected participants from elderly NSCLC patients in China.Seventy-six patients who meet the inclusion criteria will be allocated into two groups, which will receive treatments of 3-week single-agent chemotherapy with TCM or placebo for four cycles.Progression-free survival(PFS) is the primary end point, and the secondary end points are overall survival, objective response rate, time-to-progression, and quality of life(EORTC QLQ-LC43, and TCM syndrome score).Mean while, other end points such as toxicity, side effects and safety of the treatments will be assessed.DISCUSSION: Results from this study may provide evidence on the effectiveness, and parameters for the usage of single-agent chemotherapy combined with or without TCM on PFS of elderly patients with NSCLC.TRIAL REGISTRATION: ClinicalTrials.gov.(Identifier: NCT01780181).     

Anti-cancer properties of terpenoids isolated from Rhizoma Curcumae - A review

Ethnopharmacological relevance

Rhizoma Curcumae is a popular type of traditional Chinese medicine whose essential oils are widely used in the treatment of cancer in China. This review aims to systematically summarize and analyze the anti-cancer properties of terpenoids, the main components of essential oils in Rhizoma Curcumae, and thus enable the development of new anti-cancer drugs.

Materials and methods

Information on the recent progress of anti-cancer studies on terpenoids isolated from Rhizoma Curcumae, including β-elemene, δ-elemene, furanodiene, furanodienone, curcumol, and germacrone, was gathered and analyzed.

Results

Among these terpenoids, β-elemene is the most widely studied, whereas δ-elemene, furanodiene, furanodienone, curcumol, and germacrone have just recently attracted the attention of researchers. The anti-cancer effects of these terpenoids are related to the retardation of cell cycle arrest, the induction of apoptosis, and the inhibition of metastasis or tissue invasion, among others.

Conclusions

Most studies have focused on the in vitro data, and in vivo data is urgently needed. Further insight into the anti-cancer activity and the molecular basis of these compounds, combined with efforts in pharmaceutical chemistry and/or pharmaceutics, will potentially enable the development of new anti-cancer agents.     

Evidence-based toxicity evaluation and scheduling of Chinese herbal medicines

Ethnopharmacological relevance

While there is an increasing number of toxicity report cases and toxicological studies on Chinese herbal medicines, the guidelines for toxicity evaluation and scheduling of Chinese herbal medicines are lacking.

Aim

The aim of this study was to review the current literature on potentially toxic Chinese herbal medicines, and to develop a scheduling platform which will inform an evidence-based regulatory framework for these medicines in the community.

Materials and methods

The Australian and Chinese regulations were used as a starting point to compile a list of potentially toxic herbs. Systematic literature searches of botanical and pharmaceutical Latin name, English and Chinese names and suspected toxic chemicals were conducted on Medline, PubMed and Chinese CNKI databases.

Results

Seventy-four Chinese herbal medicines were identified and five of them were selected for detailed study. Preclinical and clinical data were summarised at six levels. Based on the evaluation criteria, which included risk–benefit analysis, severity of toxic effects and clinical and preclinical data, four regulatory classes were proposed: Prohibited for medicinal usage, which are those with high toxicity and can lead to injury or death, e.g., aristolochia; Restricted for medicinal usage, e.g., aconite, asarum, and ephedra; Required warning label, e.g., coltsfoot; and Over-the-counter herbs for those herbs with a safe toxicity profile.

Conclusion

Chinese herbal medicines should be scheduled based on a set of evaluation criteria, to ensure their safe use and to satisfy the need for access to the herbs. The current Chinese and Australian regulation of Chinese herbal medicines should be updated to restrict the access of some potentially toxic herbs to Chinese medicine practitioners who are qualified through registration.     

Current applications of molecular imaging and luminescence-based techniques in traditional Chinese medicine

Ethnopharmacological relevance

Traditional Chinese medicine (TCM), which is fundamentally different from Western medicine, has been widely investigated using various approaches. Cellular- or molecular-based imaging has been used to investigate and illuminate the various challenges identified and progress made using therapeutic methods in TCM. Insight into the processes of TCM at the cellular and molecular changes and the ability to image these processes will enhance our understanding of various diseases of TCM and will provide new tools to diagnose and treat patients.

Materials and methods

Various TCM therapies including herbs and formulations, acupuncture and moxibustion, massage, Gua Sha, and diet therapy have been analyzed using positron emission tomography, single photon emission computed tomography, functional magnetic resonance imaging and ultrasound and optical imaging. These imaging tools have kept pace with developments in molecular biology, nuclear medicine, and computer technology.

Results

We provide an overview of recent developments in demystifying ancient knowledge - like the power of energy flow and blood flow meridians, and serial naturopathies - which are essential to visually and vividly recognize the body using modern technology.

Conclusions

In TCM, treatment can be individualized in a holistic or systematic view that is consistent with molecular imaging technologies. Future studies might include using molecular imaging in conjunction with TCM to easily diagnose or monitor patients naturally and noninvasively.     

Triptolide: Progress on research in pharmacodynamics and toxicology

Ethnopharmacological relevance

Tripterygium wilfordii Hook. f. (Tripterygium wilfordii), also known as Huangteng and gelsemium elegan, is a traditional Chinese medicine that has been marketed in China as Tripterygium wilfordii glycoside tablets. Triptolide (TP), an active component in Tripterygium wilfordii extracts, has been used to treat various diseases, including lupus, cancer, rheumatoid arthritis and nephritic syndrome. This review summarizes recent developments in the research on the pharmacodynamics, pharmacokinetics, pharmacy and toxicology of TP, with a focus on its novel mechanism of reducing toxicity. This review provides insight for future studies on traditional Chinese medicine, a field that is both historically and currently important.

Materials and methods

We included studies published primarily within the last five years that were available in online academic databases (e.g., PubMed, Google Scholar, CNKI, SciFinder and Web of Science).

Results

TP has a long history of use in China because it displays multiple pharmacological activities, including anti-rheumatism, anti-inflammatory, anti-tumor and neuroprotective properties. It has been widely used for the treatment of various diseases, such as rheumatoid arthritis, nephritic syndrome, lupus, Behcet?s disease and central nervous system diseases. Recently, numerous breakthroughs have been made in our understanding of the pharmacological efficacy of TP. Although TP has been marketed as a traditional Chinese medicine, its multi-organ toxicity prevents it from being widely used in clinical practice.

Conclusions

Triptolide, a biologically active natural product extracted from the root of Tripterygium wilfordii, has shown promising pharmacological effects, particularly as an anti-tumor agent. Currently, in anti-cancer research, more effort should be devoted to investigating effective anti-tumor targets and confirming the anti-tumor spectrum and clinical indications of novel anti-tumor pro-drugs. To apply TP appropriately, with high efficacy and low toxicity, the safety and non-toxic dose range for specific target organs and diseases should be determined, the altered pathways and mechanisms of exposure need to be clarified, and an early warning system for toxicity needs to be established. With further in-depth study of the efficacy and toxicity of TP, we believe that TP will become a promising multi-use drug with improved clinical efficacy and safety in the future.     

Chinese herbal medicine for chronic heart failure: a multicenter,randomized, double-blind,placebo-controlled trial

ObjectiveThe purpose of this study was to assess the efficacy and safety of Chinese herbal medicine (CHM) in the treatment of chronic heart failure (CHF) patients according to syndrome differentiation.MethodsIn this multicenter, randomized, double-blind, placebo-controlled clinical trial, a total of 220 CHF patients were assigned to receive CHM or placebo granules without decoction according to syndrome differentiation in addition to their standard western treatment for 4 weeks. The change in the left ventricular ejection fraction (LVEF) was the primary outcome, and the changes in the TCM syndrome scores (TCM-SS) and New York Heart Association functional classification (NYHA-FC) were the secondary outcomes.ResultsAfter 4 weeks of treatment, the mean changes in the LVEF (13.1 ± 9.78 vs. 7.34 ± 7.40, P < 0.001) and the TCM syndrome scores (−34.2 ± 24.6 vs. −23.5 ± 25.2, P = 0.002) were better in the CHM group than in the placebo group. After two weeks of treatment, the mean changes in the LVEF (9.26 ± 7.83 vs. 4.72 ± 5.60, P < 0.001) and the TCM syndrome scores (−23.5 ± 18.6 vs. −14.0 ± 15.9, P < 0.001) were better in the CHM group than in the placebo group. In addition, repeated-measures analysis of variance (ANOVA) indicated significant time course effects of CHM versus placebo in the LVEF and TCM syndrome cores (P < 0.001 for all). The distention of the jugular vein (P = 0.021), expectoration (P = 0.044), abdominal distention (P = 0.004), and rib pain (P = 0.005) were significantly less in the CHM group than in the placebo group after two weeks of treatment. Fatigue (P = 0.001), less gas and lazy words (P = 0.001), dizziness (P = 0.003), gasping for breath (P = 0.027), abdominal distention (P = 0.011), nausea (P = 0.001) and emesis (P = 0.012) were significantly less in the CHM group than in the placebo group after treatment for four weeks. After four weeks of treatment, the change in the NYHA functional classification in the CHM group was better than that in the placebo group (P < 0.001). There was one death in the placebo group, and one patient in the CHM group experienced atrial fibrillation.ConclusionCHM treatment according to syndrome differentiation effectively improved the LVEF, TCM-SS, and NYHA-FC in patients with CHF and also appeared to be safe. Thus, CHM treatment could be used as an adjuvant therapy in the treatment of CHF (Clinical trial registration: NCT01939236).     

In vitro & in vivo assessment of a herbal formula used topically for bone fracture treatment

Aim of the study

A novel topical paste used for fracture healing (FH), consisting of the extracts of six herbs, Radix Dipsaci, Ramulus Sambucus Williamsii, Rhizoma Notoginseng, Flos Carthami, Rhizoma Rhei and Fructus Gardeniae, was developed according to the classical theory of traditional Chinese medicine. This study aimed to determine the effectiveness of this formula, and some of its important chemical components in the promotion of fracture healing. The transdermal transport of FH was also examined.

Materials and methods

The osteogenic, angiogenic and nitric oxide suppressing effects of FH and its important chemical marker components were assessed by using osteoblastosacroma UMR-106 cells, human umbilical vein endothelial cells (HUVEC) and murine macrophage RAW264.7 cells, respectively. The bone healing effects of the FH paste and its transdermal absorption were determined using a rabbit fracture model. The callus sizes, bone specific alkaline phosphatase levels and biomechanical properties of the healed bone were assessed.

Results

FH significantly increased the cell proliferation in UMR-106 and HUVEC cells and inhibited the nitric oxide production in murine macrophage in dose-dependent manner. Its important chemical components asperosaponin VI, ginsenoside Rg1 and emodin were shown to be acting positively in the respective in vitro studies. FH paste significantly improved the bone healing in the rabbit fracture model, as was indicated by the increases in callus size at weeks 2-5, and the elevations in bone specific alkaline phosphatase activities at weeks 5-6. The analysis using LC/MS/MS also showed the presence of important chemical marker components of the FH formula in the plasma after 8 weeks of topical treatment.

Conclusion

This study presents the first scientific evidence of the efficacy of a herbal paste in the promotion of fracture healing. There were evidences of transdermal transport of the chemical components, control the inflammation through nitric oxide inhibition, promotion of angiogenesis, and bone healing in the in vitro tests, as well as in the experimental animal.