Conducting research in herbal and complementary medicine

This paper outlines information and advice on how a practitioner can formally pursue research pertaining to herbal or complementary medicine. It recommends five practical steps: get advice and acquire skills, find out what other people have done already, consider what research you want to do, decide on a design and finalise a detailed research plan. Enrolling in a postgraduate research degree program is recommended as a way to acquire basic research skills and obtain support for an initial project.

Adjuvant use of nutritional and herbal medicines with antidepressants, mood stabilizers and benzodiazepines

Adjuvant use of nutritional and herbal medicines has potential to increase the efficacy of synthetic pharmaceuticals, and perhaps also decrease their side-effects by allowing lower doses to be prescribed. We evaluated current evidence for adjuvant use of nutritional and herbal medicines with antidepressants, mood stabilizers and benzodiazepines; and explored novel future areas of research. The paper also critiques current evidence for co-administration of St. John’s wort with synthetic antidepressants. We performed a systematic search of MEDLINE, CINAHL, PsycINFO, The Cochrane database, China National Knowledge Infrastructure and the Chinese Science Citation Database. Search results were supplemented by a review of reference lists and a forward search using the Web of Science. Where possible we calculated effect sizes. Encouraging evidence exists for the use of omega-3 fatty acids, SAMe, folic acid and l-tryptophan adjuvantly with antidepressants to enhance response and improve efficacy. Various nutrients also have emerging evidence as effective adjuncts with antipsychotics and mood stabilizers. While some evidence supports nutritional adjuvancy with various psychopharmacotherapies, adjuvant use of herbal therapies has not been sufficiently studied to warrant standard clinical application. This remains a promising area of research via robust, safety-conscious studies.

A randomized controlled pilot study comparing aqueous cream with a beeswax and herbal oil cream in the provision of relief from postburn pruritis

Postburn itch is reported to affect up to 87% of the burn population. Although treatments for postburn itch are multimodal, they remain consistently ineffective. However, recent anecdotal evidence from several outpatients at a tertiary referral hospital suggests that a cream combining beeswax and several herbal oils may be effective in the minimization of postburn itch. The aim of this study was to test the efficacy of beeswax and herbal oil cream against the standard treatment of aqueous cream in the provision of relief from the symptoms of postburn itch. A randomized controlled trial compared two groups using a visual analog scale, frequency of cream application, itch recurrence after cream application, use of antipruritic medications, and sleep disturbance to determine the effect of itch severity and duration. Fifty-two participants were enrolled in the study (84% male) with a mean age of 35 years (SD = 16) and mean burn TBSA of 7.2% (SD = 7.7). Study results found that the beeswax and herbal oil cream reduce itch after application more frequently than aqueous cream (P = .001). In addition, when managed with beeswax and herbal oil cream, participants found that their itch recurred later (P ≤ .001) and their use of antipruritic medications was lower (P = .023). Findings of this study suggest beeswax and herbal oil cream to be more effective in the minimization of postburn itch than aqueous cream. Given this, a larger study examining the efficacy of beeswax and herbal oil cream appears warranted.

Pharmacokinetic studies of a Chinese triple herbal drug formula

Yin Chen Hao Tang preparation (YCHTP) is a classic traditional Chinese medicine formula, which is commonly used for clinical treatment of hepatological diseases. In this study, a rapid and validated high-performance liquid chromatography (HPLC) method was developed to simultaneously identify 6,7-dimethylesculetin and geniposide in rat plasma. This assay was performed on a Dikma Diamonsil RP(18) column (200 mmx4.6 mm, 5 mum) with acetonitrile-methanol-water (0.1% formic acid) as the mobile phase, showing acceptable linearity, intra- and inter-day precision and accuracy (R.S.D.=5%), and absolute recovery for two analytes (74%); the limits of quantitation were 0.4 and 1.12 mug/ml, and the limits of detection were 0.06 and 0.09 mug/ml for two analytes. The developed method was successfully applied to study the effect of formula compatibility on the pharmacokinetics of 6,7-dimethylesculetin and geniposide in YCHTP when orally administrating an effective human daily dose of YCHTP to rats. We surmise that formula compatibility can significantly influence the pharmacokinetics of YCHTP, and we have elucidated and validated the compatible administration of YCHTP.

Biological values of acupuncture and Chinese herbal medicine : impact on the life science

Editorial paper

Investigating the potential of Shikonin, a Chinese herbal medicine, as a novel scar remediation therapy

This project investigates for the first time the biological mechanisms underlying the anecdotal use of Shikonin, an active component extracted from the Chinese herbal medicine "Zi Cao", as a treatment for hypertrophic scars. Compelling molecular and cellular evidence was generated supporting the therapeutic value of Shikonin as a scar treatment, suggesting that further development of this agent is warranted.

St. John’s wort and Kava in treating major depressive disorder with comorbid anxiety : a randomised double-blind placebo-controlled pilot trial

Objective - We report the first randomised controlled trial (RCT) using a combination of St. John’s wort (SJW) and Kava for the treatment of major depressive disorder (MDD) with comorbid anxiety. Methods - Twenty-eight adults with MDD and co-occurring anxiety were recruited for a double-blind RCT. After a placebo run-in of 2 weeks, the trial had a crossover design testing SJW and Kava against placebo over two controlled phases, each of 4 weeks. The primary analyses used intention-to-treat and completer analyses. Results - On both intention-to-treat ( p¼0.047) and completer analyses ( p¼0.003), SJW and Kava gave a significantly greater reduction in self-reported depression on the Beck Depression Inventory (BDI-II) over placebo in the first controlled phase. However, in the crossover phase, a replication of those effects in the delayed medication group did not occur. Nor were there significant effects on anxiety or quality of life. Conclusion - There was some evidence of antidepressant effects using SJW and Kava in a small sample with comorbid anxiety. Possible explanations for the absence of anxiolysis may include a potential interaction with SJW, the presence of depression, or an inadequate dose of Kava.

The Kava Anxiety Depression Spectrum Study (KADSS): A randomized, placebo-controlled, cross-over trial using an aqueous extract of Piper methysticum.

Rationale: Piper methysticum (Kava) has been withdrawn in European, British, and Canadian markets due to concerns over hepatotoxic reactions. The WHO recently recommended research into “aqueous” extracts of Kava. Objective: The objective of this study was to conduct the first documented human clinical trial assessing the anxiolytic and antidepressant efficacy of an aqueous extract of Kava. Design and participants: The Kava Anxiety Depression Spectrum Study was a 3-week placebo-controlled, double-blind crossover trial that recruited 60 adult participants with 1 month or more of elevated generalized anxiety. Five Kava tablets per day were prescribed containing 250 mg of kavalactones/day. Results: The aqueous extract of Kava reduced participants' Hamilton Anxiety Scale score in the first controlled phase by −9.9 (CI = 7.1, 12.7) vs. −0.8 (CI = −2.7, 4.3) for placebo and in the second controlled phase by −10.3 (CI = 5.8, 14.7) vs. +3.3 (CI = −6.8, 0.2). The pooled effect of Kava vs. placebo across phases was highly significant (p < 0.0001), with a substantial effect size (d = 2.24, η² [sub]p[sub] = 0.428). Pooled analyses also revealed highly significant relative reductions in Beck Anxiety Inventory and Montgomery–Asberg Depression Rating Scale scores. The aqueous extract was found to be safe, with no serious adverse effects and no clinical hepatotoxicity. Conclusions: The aqueous Kava preparation produced significant anxiolytic and antidepressant activity and raised no safety concerns at the dose and duration studied. Kava appears equally effective in cases where anxiety is accompanied by depression. This should encourage further study and consideration of globally reintroducing aqueous rootstock extracts of Kava for the management of anxiety.

Kava and St. John's wort : current evidence for use in mood and anxiety disorders

Background: Mood and anxiety disorders pose significant health burdens on the community. Kava and St John’s wort (SJW) are the most commonly used herbal medicines in the treatment of anxiety and depressive disorders, respectively. Objectives: To conduct a comprehensive review of kava and SJW, to review any evidence of efficacy, mode of action, pharmacokinetics, safety and use in Major Depressive Disorder (MDD), Bipolar Disorder (BP), Seasonal Affective Disorder (SAD), Generalized Anxiety Disorder (GAD), Social Phobia (SP), Panic Disorder (PD), Obsessive-Compulsive Disorder (OCD), and Post Traumatic Stress Disorder (PTSD). Methods: A systematic review was conducted using the electronic databases MEDLINE, CINAHL, and The Cochrane Library during late 2008. The search criteria involved mood and anxiety disorder search terms in combination with kava, Piper methysticum, kavalactones, St John’s wort, Hypericum perforatum, hypericin and hyperforin. Additional search criteria for safety, pharmacodynamics , and pharmacokinetics was employed. A subsequent forward search was conducted of the papers using Web of Science cited reference search. Results: Current evidence supports the use of SJW in treating mild-moderate depression, and for kava in treatment of generalized anxiety. In respect to the other disorders, only weak preliminary evidence exists for use of SJW in SAD. Currently there is no published human trial on use of kava in affective disorders, or in OCD, PTSD, PD or SP. These disorders constitute potential applications that warrant exploration. Conclusions: Current evidence for herbal medicines in the treatment of depression and anxiety only supports the use of Hypericum perforatum for depression, and Piper methysticum for generalized anxiety.

An explorative qualitative analysis of participants' experience of using kava versus placebo in an RCT. (Clinical report)

Many randomised controlled trials (RCT) have been conducted using Piper methysticum (kava), however no qualitative research exploring the experience of taking kava during a clinical trial has previously been reported. ---------- Patients and methods: A qualitative research component (in the form of semi structured and open ended written questions) was incorporated into an RCT to explore the experiences of those participating in a clinical trial of kava. The written questions were provided to participants at weeks 2 and 3 (after randomisation, after each controlled phase). The researcher and participants were blinded as to whether they were taking kava or placebo. Two open ended questions were posed to elucidate their experiences from taking either kava or placebo. Thematic analysis was undertaken and researcher triangulation employed to ensure analytical rigour. Key themes after the kava phases were a reduction in anxiety and stress, and calming or relaxing mental effects. Other themes related to improvement in sleep and in somatic anxiety symptoms. ---------- Results: Kava use did not cause any serious adverse reactions although a few respondents reported nausea or other gastrointestinal side effects. This represents the first documented qualitative investigation of the experience of taking kava during a clinical trial. The primary themes involved anxiolytic and calming effects, with only a minor theme reflecting side effects. Our exploratory qualitative data was consistent with the significant quantitative results revealed in the study and provides additional support to suggest the trial results did not exclude any important positive or negative effects (at least as experienced by the trial participants).

Plant-made therapeutics: An emerging platform in South Africa

The field of plant-made therapeutics in South Africa is well established in the form of exploitation of the country's considerable natural plant diversity, both in the use of native plants in traditional herbal medicines over many centuries, and in the more modern extraction of pharmacologically-active compounds from plants, including those known to traditional healers. In recent years, this has been added to by the use of plants for the stable or transient expression of pharmaceutically-important compounds, largely protein-based biologics and vaccines. South Africa has a well-developed plant biotechnology community, as well as a comprehensive legislative framework for the regulation of the exploitation of local botanic resources, and of genetically-modified organisms. The review explores the investigation of both conventional and recombinant plants for pharmaceutical use in South Africa, as well as describing the relevant legislative and regulatory frameworks. Potential opportunities for national projects, as well as factors limiting biopharming in South Africa are discussed. © 2011.

Thyroxine and reserpine-induced changes in metabolic profiles of rat urine and the therapeutic effect of Liu Wei Di Huang Wan detected by UPLC-HDMS

The promise of metabonomics, a new "omics" technique, to validate Chinese medicines and the compatibility of Chinese formulas has been appreciated. The present study was undertaken to explore the excretion pattern of low molecular mass metabolites in the male Wistar-derived rat model of kidney yin deficiency induced with thyroxine and reserpine as well as the therapeutic effect of Liu Wei Di Huang Wan (LW) and its separated prescriptions, a classic traditional Chinese medicine formula for treating kidney yin deficiency in China. The study utilized ultra-performance liquid chromatography/electrospray ionization synapt high definition mass spectrometry (UPLC/ESI-SYNAPT-HDMS) in both negative and positive electrospray ionization (ESI). At the same time, blood biochemistry was examined to identify specific changes in the kidney yin deficiency. Distinct changes in the pattern of metabolites, as a result of daily administration of thyroxine and reserpine, were observed by UPLC-HDMS combined with a principal component analysis (PCA). The changes in metabolic profiling were restored to their baseline values after treatment with LW according to the PCA score plots. Altogether, the current metabonomic approach based on UPLC-HDMS and orthogonal projection to latent structures discriminate analysis (OPLS-DA) indicated 20 ions (14 in the negative mode, 8 in the positive mode, and 2 in both) as "differentiating metabolites".

Metabolic urinary profiling of alcohol hepatotoxicity and intervention effects of Yin Chen Hao Tang in rats using ultra-performance liquid chromatography/electrospray ionization quadruple time-of-flight mass spectrometry

This paper was designed to study metabonomic characters of the hepatotoxicity induced by alcohol and the intervention effects of Yin Chen Hao Tang (YCHT), a classic traditional Chinese medicine formula for treatment of jaundice and liver disorders in China. Urinary samples from control, alcohol- and YCHT-treated rats were analyzed by ultra-performance liquid chromatography/electrospray ionization quadruple time-of-flight mass spectrometry (UPLC/ESI-QTOF-MS) in positive ionization mode. The total ion chromatograms obtained from the control, alcohol- and YCHT-treated rats were easily distinguishable using a multivariate statistical analysis method such as the principal components analysis (PCA). The greatest difference in metabolic profiling was observed from alcohol-treated rats compared with the control and YCHT-treated rats. The positive ions m/z 664.3126 (9.00 min) was elevated in urine of alcohol-treated rats, whereas, ions m/z 155.3547 (10.96 min) and 708.2932 (9.01 min) were at a lower concentration compared with that in urine of control rats, however, these ions did not indicate a statistical difference between control rats and YCHT-treated rats. The ion m/z 664.3126 was found to correspond to ceramide (d18:1/25:0), providing further support for an involvement of the sphingomyelin signaling pathway in alcohol hepatotoxicity and the intervention effects of YCHT.

Simultaneous determination by UPLC-ESI-MS of scoparone, capillarisin, rhein, and emodin in rat urine after oral administration of Yin Chen Hao Tang preparation

A simple, sensitive, and validated method was developed for simultaneous determination of scoparone, capillarisin, rhein, and emodin in rat urine by ultra-performance liquid chromatography/electrospray ionization quadruple time-of-flight mass spectrometry (UPLC-MS). The urinary samples were analyzed on an Acquity UPLC BEH C18 1.7 microm 2.1x50 mm column. Scoparone, capillarisin, rhein, and emodin in rat urine were simultaneously analyzed with good separation. The lower limits of detection were 6.0, 9.0, 7.0, and 3.0 ng/mL, and the lower limits of quantification were 20.0, 33.0, 24.0, and 12.0 ng/mL for scoparone, capillarisin, rhein, and emodin, respectively. The intra- and inter-day precisions (RSD) were less than 9%. The intra- and inter-accuracies were found to be in the range of 94.14-104.54% for scoparone, 101.72-107.34% for capillarisin, 95.24-103.59% for rhein, and 101.32-107.82% for emodin at three concentration levels. The absolute recoveries for scoparone, capillarisin, rhein, and emodin were not less than 77.0%. The developed method has been applied to determine scoparone, capillarisin, rhein, and emodin in rat urine after oral administration of Yin Chen Hao Tang preparation, a traditional Chinese medicine formulation widely used in China for treatment of jaundice and liver disorders.

Protective effects of sweroside on human MG-63 cells and rat osteoblasts

Herbal Fructus Corni is a folk medicine with a long history of safe use for treating osteoporosis in postmenopausal women or elderly men in Asia. Sweroside is a bioactive herbal ingredient isolated from Fructus Corni, which has been widely used for the treatment of osteoporosis in traditional Chinese medicine (TCM). Unfortunately, the working mechanisms of this compound are difficult to determine and thus remain unclear. The aim of the study was performed to determine the potential molecular mechanism of the anti-osteoporotic effect of sweroside on the human MG-63 cells and rat osteoblasts. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test was used to observe the effect of sweroside on cell proliferation. The activity of alkaline phosphatase (ALP) and the amount of osteocalcin were also assayed the cell differentiation. Sweroside significantly increased the proliferation of human MG-63 cells and rat osteoblasts (P<0.01). It increased the activity of ALP, and osteocalcin was also elevated in response to sweroside (P<0.05). Of note, flowcytometer assay showed that sweroside can attenuate and inhibit apoptosis. Sweroside has a direct osteogenic effect on the proliferation and differentiation of cultured human MG-63 cells and rat osteoblasts in vitro. These data will help in understanding the molecular mechanisms of therapeutic efficacy of sweroside, and highlight insights into drug discovery. In the current study, sweroside has been suggested to be a promising osteoporosis therapeutic natural product.