Traditional Chinese Medicine (TCM) is characterized by the wide use of herbal formulae, which are capable of systematically treating diseases determined by interactions among various herbs. However, the combination rule of TCM herbal formulae remains a mystery due to the lack of appropriate methods.
From a network perspective, we established a method called Distance-based Mutual Information Model (DMIM) to identify useful relationships among herbs in numerous herbal formulae. DMIM combines mutual information entropy and “between-herb-distance” to score herb interactions and construct herb network. To evaluate the efficacy of the DMIM-extracted herb network, we conducted in vitro assays to measure the activities of strongly connected herbs and herb pairs. Moreover, using the networked Liu-wei-di-huang (LWDH) formula as an example, we proposed a novel concept of “co-module” across herb-biomolecule-disease multilayer networks to explore the potential combination mechanism of herbal formulae.
DMIM, when used for retrieving herb pairs, achieves a good balance among the herb’s frequency, independence, and distance in herbal formulae. A herb network constructed by DMIM from 3865 Collaterals-related herbal formulae can not only nicely recover traditionally-defined herb pairs and formulae, but also generate novel anti-angiogenic herb ingredients (e.g. Vitexicarpin with IC50=3.2 μM, and Timosaponin A-III with IC50=3.4 μM) as well as herb pairs with synergistic or antagonistic effects. Based on gene and phenotype information associated with both LWDH herbs and LWDH-treated diseases, we found that LWDH-treated diseases show high phenotype similarity and identified certain “co-modules” enriched in cancer pathways and neuro-endocrine-immune pathways, which may be responsible for the action of treating different diseases by the same LWDH formula.
DMIM is a powerful method to identify the combination rule of herbal formulae and lead to new discoveries. We also provide the first evidence that the co-module across multilayer networks may underlie the combination mechanism of herbal formulae and demonstrate the potential of network biology approaches in the studies of TCM.
Traditional Chinese medicine (TCM) treatments are often prescribed based on individuals' pattern diagnoses. A systematic review of Chinese and English literatures on TCM pattern differentiation, treatment principle, and pattern-based treatment for insomnia has therefore been conducted. A total of 227 studies, 17916 subjects, and 87 TCM patterns were analyzed. There was a limited consistency in pattern-based TCM treatment of insomnia across practitioners. Except for Gui Pi Tang, An Shen Ding Zhi Wan, and Wen Dan Tang which were used more commonly for deficiency of both the heart and spleen, internal disturbance of phlegm-heat, and qi deficiency of the heart and gallbladder, respectively, the selection of herbal formula for other patterns and pattern-based prescription of individual herbs and acupoints were not consistent. Suanzaoren (Semen Z. spinosae), Fuling (Poria), Yejiaoteng (Caulis P. multiflori), Gancao (Radix Glycyrrhizae), Baishao (Radix P. alba), Shenmen (HT7), Yintang (EX-HN3), Sanyinjiao (SP6), Baihui (GV20), Anmian (EX-HN22), and Sishencong (EX-HN1) were commonly used, but nonspecifically for many patterns. Treatment principles underlying herb and acupoint selection were seldom reported. Although many studies were reviewed, the study quality and diagnostic process were inadequate. More high quality studies are needed to examine the additional benefits of pattern differentiation and pattern-based TCM treatment.
Yukmijihwang-tang, a traditional herbal formula, has been used for treating disorder, diabetic mellitus and neurosis in China (Liu-wei-di-huang-tang in Chinese), Japan (Lokumijio-to in Japanese) and Korea for many years. In this study, we investigated the effects of Yukmijihwang-tang water extract (YJT) on the development of benign prostatic hyperplasia (BPH) using a rat model of testosterone propionate (TP)-induced BPH.
A total of 30 rats were divided into five groups. One group was used as a control and the other groups received subcutaneous injections of TP for 4 weeks to induce BPH. YJT (200 or 400 mg/kg) was administered daily for 4 weeks to two groups by oral gavage concurrently with the TP. The animals were euthanized, the prostate and body weights were recorded, and tissues were subjected to hormone assays and histomorphology. In addition, we investigated proliferating cell nuclear antigen (PCNA) expression in the prostate using immunoblotting.
Animals with BPH showed significantly increased absolute and relative prostate weights, increased dihydrotestosterone levels in the serum or prostate and increased PCNA expression in the prostate; however, YJT-treated animals showed significant reductions compared with the animals with TP-induced BPH. Histomorphology also showed that YJT inhibited TP-induced prostatic hyperplasia.
These findings indicate that YJT effectively inhibited the development of BPH and might be a useful drug clinically.
Yukmijihwang-tang; Traditional herbal formula; Benign prostatic hyperplasia; Dihydrotestosterone
Hypertension is a clinical common disease, with high mortality and disability. Although there have also been significant advances in therapeutic concepts and measures, it has shown a certain value and significance in the treatment of Chinese medicine. The control strategy on hypertension is described from the following aspects such as differentiation of symptoms, pathogenesis, formula syndrome, and herb syndrome. As the common clinical manifestations of hypertension are dizziness, headache, fatigue, lassitude in the loins and knees, and so on, the pathogeneses of them are analysed. The author found that the main pathogenesis of the disease is heat, excessive fluid, and deficiency, which occurred incorporatively and interacted with each other in patients. Although the pathogenesis of the disease is complicated, the distribution of formula syndromes and herb syndromes is regular. The common formula syndromes include Banxia Baishu Tianma Tang (Decoction of Pinellia ternata, Atractylodes and Gastrodia elata), Da Chaihu Tang (Major Bupleurum Decoction), and Liu Wei Dihuang Wan (Pill of Rehmannia). And the common herb syndromes include Tian Ma (Gastrodia elata) syndrome, Sheng Di Huang (Radix Rehmanniae) syndrome, Niu Xi (Achyranthes Root) syndrome, and Chuan Xiong (Ligusticum wallichii) syndrome.
San-Huang-Xie-Xin-Tang (SHXXT), a widely used Chinese herbal formula, consists of rhizomes of Rheum officinale, roots of Scutellaria baicalensis and rhizomes of Coptis chinesis. This study investigated the metabolism and pharmacokinetics of polyphenols in SHXXT, including baicalin, baicalein, wogonin, emodin, aloe-emodin, rhein and chrysophanol. The quantitation methods of SHXXT decoction and rat serum using high performance liquid chromatography were developed and validated in this study. After oral administration of SHXXT decoction to rats, the parent forms of various constituents and their conjugated metabolites in serum were determined before and after hydrolysis with β-glucuronidase and sulfatase. The results showed that only free form of rhein can be quantitated, whereas the parent forms of coptisine, palmatine, berberine, baicalein, wogonin, emodin, aloe-emodin and chrysophanol were not detected in serum. The glucuronides of baicalein, wogonin, emodin, aloe-emodin, rhein and chrysophanol were the predominant forms in bloodstream. In order to evaluate the in vivo antioxidant activity of SHXXT, the serum metabolite of SHXXT was prepared, characterized and followed by evaluation of the effect on AAPH-induced hemolysis. The results indicated that metabolites of SHXXT exhibited significant free radical scavenging activity. We suggest that biologists redirect their focus to the bioactivity of the conjugated metabolites of these polyphenols.
Lung cancer has long been one of the most deadly forms of cancer. The majority of lung cancers are of the non-small-cell lung cancer (NSCLC) type. Here we used the non-small-cell lung carcinoma cell line A549 to screen 15 different traditional Chinese herbal medicine (CHM) formulae to explore the possible mechanisms of alternative medicine in lung cancer therapy. We identified three formulae (Formulae 3, 5, and 14) that substantially decreased the survival of A549 cells but did not affect MRC5 normal lung tissue cells. Formula 14, Yang-Dan-Tang, a modified decoction of Ramulus Cinnamomi Cassiae, was chosen for further characterization. Flow cytometry analysis showed that treatment of Formula 14 induced cell cycle arrest in G1 and G2 phase without causing significant cell death. These results were also confirmed by Western blot analysis, with decreased expression of G1/S and G2/M promoting cell cycle machinery including cyclin D3, cyclin B1, CDK4, and CDK6. This study provides further insight into the possible working mechanism of Yang-Dan-Tang in patients.
In traditional Chinese medicine theory (TCM), the affected parts of sprains, bruises and arthritis are considered to be under certain conditions of TCM concept. We administered two Kampo medicines with synergistic effects to promote quick recovery from these conditions. Jidabokuippo (Zhidapuyifang in Chinese), which means ‘decoction for contusions’ is expected to remove these conditions. Hachimijiogan (Baweidihuangwan in Chinese), which translates as ‘eight-ingredient pill with Rehmannia’ is expected to restore presumed minute bone injury and regulates bone metabolism by changing such conditions based on TCM theory. We administered the two prescriptions to 10 patients (age range: 40–85 years; 1 male, 9 females) suffering from bruises, sprains, arthritis and spinal compression fracture without changing their routine intake of other drugs. Patients reported on changes in the pain of affected body parts by using the visual analog scale (VAS) before and after administration of Kampo medicine. In almost all cases, recovery began promptly after administration and the pain disappeared within ∼2 weeks. Large doses for a short time brought about much quicker recovery than small doses. Administration of a combination of two Kampo medicines, Jidabokuippo and Hachimijiogan, quickly resolved the pain of bruises, sprains, arthritis and one spinal compression fracture.
bruise; Kampo; pain; sprain
The objective of this clinical study is to examine the effects of a Chinese herbal medicine formula (Jia Wei Liu Jun Zi Tang: JWLJZT) on motor and non-motor symptoms, and on complications of conventional therapy in idiopathic Parkinson's disease (PD), using an add-on design. Fifty-five patients with PD were randomly allocated to receive either Chinese herbal medicine or placebo for 24 weeks. Primary outcome measure was the 39-item Parkinson's Disease Questionnaire (PDQ-39). Secondary outcome measures included the Unified Parkinson's Disease Rating Scale (UPDRS), Short-Form-36 Health Survey (SF-36), Geriatric Depression Scale (GDS), home diaries, and a range of category rating scales. JWLJZT resulted in a significant improvement in the UPDRS IVC when compared with placebo at 12 weeks (P = .039) and 24 weeks (P = .034). In addition, patients in the Chinese herbal medicine group also showed significant improvement in PDQ-39 communication scores at 12 weeks (P = .024) and 24 weeks (P = .047) when compared with the placebo group. There were no significant differences between treatment and control groups for SF-36 variables, GDS score or the mean daily “on-off” time. One case of mild diarrhea was noted in the treatment group. The findings suggest that JWLJZT can relieve some non-motor complications of conventional therapy and improve the communication ability in patients with PD. The results of this pilot study warrant larger multi-center clinical studies to assess long-term efficacy and tolerability of JWLJZT, and to elucidate the mechanisms by which it affects PD function.
Traditional Chinese herbal therapy can be characterized by the use of a large number of multi-herb formulae. To provide modern and Western scientists without knowledge of Chinese literature and cultural background easy access to information, a database with a total of 11 810 traditional Chinese herbal formulae was constructed. All the information was then translated into understandable scientific terms in English. While coining the formula titles in English, we discovered some principles governing the naming of titles by using computer analysis. In addition, we observed that about 92% of the formulae are in the range of single-herb formulae to thirteen-herb formulae. Most large number-herb formulae are formulated by combining pre-existing smaller number-herb formulae. The King herbs () with major therapeutic activity in a multi-herb formula were identified by the formulation concept using two parameters: the herbal dose and the herbal drug property (the degree of toxicity). Based on such analytical data, we established an English code system representing all formula titles written in ideographic Chinese characters: an array of important key words such as ‘Herbal name in Latin + Efficacy (Target organs) + Preparation form + Number of herbs.’ By searching the English version of the database with any of the above key words, a variety of information on the status of traditional Chinese herbal therapy can be accessed.
traditional Chinese herbal therapy; herbal database; code system; formula title
Most traditional Chinese herbal formulas consist of at least four herbs. Four-Agents-Decoction (Si Wu Tang) is a documented eight hundred year old formula containing four herbs and has been widely used to relieve menstrual discomfort in Taiwan. However, no specific effect had been systematically evaluated. We applied Western methodology to assess its effectiveness and safety for primary dysmenorrhoea and to evaluate the compliance and feasibility for a future trial.
A randomised, double-blind, placebo-controlled, pilot clinical trial was conducted in an ad hoc clinic setting at a teaching hospital in Taipei, Taiwan. Seventy-eight primary dysmenorrheic young women were enrolled after 326 women with self-reported menstrual discomfort in the Taipei metropolitan area of Taiwan were screened by a questionnaire and subsequently diagnosed by two gynaecologists concurrently with pelvic ultrasonography. A dosage of 15 odorless capsules daily for five days starting from the onset of bleeding or pain was administered. Participants were followed with two to four cycles for an initial washout interval, one to two baseline cycles, three to four treatment cycles, and three follow-up cycles. Study outcome was pain intensity measured by using unmarked horizontal visual analog pain scale in an online daily diary submitted directly by the participants for 5 days starting from the onset of bleeding or pain of each menstrual cycle. Overall-pain was the average pain intensity among days in pain and peak-pain was the maximal single-day pain intensity. At the end of treatment, both the overall-pain and peak-pain decreased in the Four-Agents-Decoction (Si Wu Tang) group and increased in the placebo group; however, the differences between the two groups were not statistically significant. The trends persisted to follow-up phase. Statistically significant differences in both peak-pain and overall-pain appeared in the first follow-up cycle, at which the reduced peak-pain in the Four-Agents-Decoction (Si Wu Tang) group did not differ significantly by treatment length. However, the reduced peak-pain did differ profoundly among women treated for four menstrual cycles (2.69 (2.06) cm, mean (standard deviation), for the 20 women with Four-Agents-Decoction and 4.68 (3.16) for the 22 women with placebo, p = .020.) There was no difference in adverse symptoms between the Four-Agents-Decoction (Si Wu Tang) and placebo groups.
Four-Agents-Decoction (Si Wu Tang) therapy in this pilot post-market clinical trial, while meeting the standards of conventional medicine, showed no statistically significant difference in reducing menstrual pain intensity of primary dysmenorrhoea at the end of treatment. Its use, with our dosage regimen and treatment length, was not associated with adverse reactions. The finding of statistically significant pain-reducing effect in the first follow-up cycle was unexpected and warrants further study. A larger similar trial among primary dysmenorrheic young women with longer treatment phase and multiple batched study products can determine the definitive efficacy of this historically documented formula.
Traditional Chinese Medicine (TCM) has a 3000 years' history of human use. A literature survey addressing traditional evidence from human studies was done, with key result that top 10 TCM herb ingredients including Poria cocos, Radix polygalae, Radix glycyrrhizae, Radix angelica sinensis, and Radix rehmanniae were prioritized for highest potential benefit to dementia intervention, related to the highest frequency of use in 236 formulae collected from 29 ancient Pharmacopoeias, ancient formula books, or historical archives on ancient renowned TCM doctors, over the past 10 centuries.
Based on the history of use, there was strong clinical support that Radix polygalae is memory improving. Pharmacological investigation also indicated that all the five ingredients mentioned above can elicit memory-improving effects in vivo and in vitro via multiple mechanisms of action, covering estrogen-like, cholinergic, antioxidant, anti-inflammatory, antiapoptotic, neurogenetic, and anti-Aβ activities. Furthermore, 11 active principles were identified, including sinapic acid, tenuifolin, isoliquiritigenin, liquiritigenin, glabridin, ferulic acid, Z-ligustilide, N-methyl-beta-carboline-3-carboxamide, coniferyl ferulate and 11-angeloylsenkyunolide F, and catalpol. It can be concluded that TCM has a potential for complementary and alternative role in treating senile dementia. The scientific evidence is being continuously mined to back up the traditional medical wisdom.
We have previously shown that arsenic-containing Chinese herbal formula, Qing-Huang powder capsule (containing tetraarsenic tetrasulfide, As4S4), is effective in the treatment of myelodysplastic syndrome (MDS); yet the underlined mechanisms remain unclear. In this study, using standard cytogenetic analysis (G-banded) and global DNA methylation method (ChIP-on-chip assays), we aimed to determine the effect of arsenic-containing Chinese herbal formula on karyotype status and the genomic methylation level in primarily diagnosed MDS patients. Correlation of aberrant DNA methylation and chromosome aberrations in MDS was also investigated. We found that the number of genes with aberrant DNA methylation was highest in MDS patients with normal karyotype, followed by trisomy 8 karyotype, and relatively low in patients with cytogenetic abnormalities other than trisomy 8. Treatment with arsenic-containing Chinese herbal formula had no effects on karyotype status, but resulted in a significant genome-wide demethylation. Our research uncovered a DNA demethylating activity of arsenic-containing Chinese herbal formula in the treatment of MDS.
AIM: To assess the antacid effects of the tonic Chinese herbal prescriptions, Si-Jun-Zi-Tang (SJZT) and Shen-Ling-Bai-Zhu-San (SLBZS).
METHODS: Decoctions of the tonic Chinese herbal prescriptions, SJZT and SLBZS, were prepared according to Chinese original documents. The pH of the prescription decoctions and their neutralizing effects on artificial gastric acids were determined and compared with water and the active controls, sodium bicarbonate and colloidal aluminum phosphate. A modified model of Vatier’s artificial stomach was used to determine the duration of consistent neutralization effect on artificial gastric acids. The neutralization capacity in vitro was determined with the titration method of Fordtran’s model.
RESULTS: The results showed that both SJZT and SLBZS have antacid effects in vitro. Compared with the water group, SJZT and SLBZS were found to possess significant gastric acid neutralizing effects. The duration for consistent neutralization of SLBZS was significantly longer than that of water. Also, SLBZS and SJZT exhibited significant antacid capacities compared to water.
CONCLUSION: SJZT and SLBZS were consistently active in the artificial stomach model and are suggested to have antacid effects similar to the active control drugs.
Traditional Chinese medicines; Antacid; Acid neutralizing capacity; Artificial stomach
San-Huang-Xie-Xin-Tang (SHXXT) decoction, a traditional Chinese medicine containing Rhei rhizome, Coptidis rhizome, and Scutellariae radix, is widely used in hepatoprotective therapy. However, preparation of the decoction requires addition of boiling water that causes loss of numerous effective components.
To improve the bioavailability of the decoction, nanoscale SHXXT was developed. Chloroform-induced liver injury and hepatic stellate cell activity in mice were used to demonstrate the hepatoprotective characteristics of nanoscale SHXXT decoction.
Liver/body weight ratio and serum aspartate and alanine aminotranferase levels were recovered by the nanoscale SHXXT. TIMP-1 gene expression was inhibited and MMP-2 gene expression was accelerated in activated hepatic stellate cells.
Nanoscale SHXXT decoction prepared in room temperature water could have preserved hepatoprotective ability. The results of this study indicate that nanoscale SHXXT could be extracted easily. The simple preparation of this herbal decoction is more convenient and energy-efficient.
Chinese herb medicine; San-Huang-Xie-Xin-Tang; nanoparticle; liver fibrosis
Rheumatoid arthritis (RA), a chronic autoimmune disease, affects sufferers in many different ways. Treatment of this chronic condition is particularly challenging. Traditional Chinese Medicine (TCM) provides alternatives. Bizhongxiao decoction (BZX) is a TCM complex, which has been used clinically for many years to treat RA. The purpose of this study is to compare the effects of BZX decoction and its dismantled formulae on IL-1 and TNF-1 levels in rats with RA, and to elucidate its mechanism of action.
Ninety healthy normal female SD rats were randomly divided into six groups: normal (control), model, BZX decoction, and the three dismantled formulae (I: heat-clearing and detoxication, II: dissipating dampness, and III: blood circulation promotion). Apart from the normal (control) group, the rats in each group were injected subcutaneously with bovine type II collagen and complete Freund adjuvant to establish a collagen-induced arthritis model, so that inhibition of foot swelling in the rats by BZX decoction and its dismantled formulae could be observed. Immunohistochemistry was used to assess the levels of the inflammatory cytokines IL-1 and TNF in synovial joints at various time points.
Twenty-one days after the model was established, the levels of TNF and IL-1 were significantly higher in the model group, BZX decoction group and dismantled formula groups I, II and III than in the normal controls (P < 0.05). The levels of these cytokines were significantly higher in the model group than the BZX decoction or the three dismantled formula groups (P <0.01). At longer times, the TNF and IL-1 levels in model group rose gradually; those in the BZX decoction and dismantled formula groups were gradually reduced. The cytokine levels in the BZX decoction group were lower than in the three dismantled formula groups and continued to decline.
BZX decoction and the three dismantled formulae examined down-regulated the inflammatory factors IL-1 and TNF in collagen-induced arthritis rat models, but BZX exerted the strongest effect.
Bizhongxiao decoction; Rheumatoid arthritis; Interleukin-1; Tumor necrosis factor
The aim of this study is to investigate the effect of Shen-qi-di-huang decoction on reducing proteinuria and to discuss the mechanism of its action in Adriamycin (ADR)-induced nephropathy rats. The rats were randomly divided into three groups (n=12 each group): normal control (group A); ADR model control (group B); ADR + Shen-qi-di-huang decoction (group C). In group B and C, the rats were intravenously injected with ADR (6.5mg/kg). The rats in group C were orally administrated with Shen-qi-di-huang decoction after the injection of ADR. On day 7, 14, 28, 56 after ADR injection, 24h urine protein was detected. On day 28, 56 after ADR injection, ALB, ALT, serum creatinine (Scr) and BUN were examined. The morphological changes of the kidneys were observed by light microscope and electron microscope on day 28, 56 after ADR injection. The expression of nephrin was determined by immunohistochemistry and RT-PCR on day 28, 56 after ADR injection. Compared with group B, 24h urine protein and Scr decreased in group C on day 56 (P<0.05). The expression of nephrin determined by immunohistochemistry and RT-PCR increased in group C on day 28, 56 (P<0.05). The morphology observed by light microscope and electron microscope improved in group C on day 28, 56. Shen-qi-di-huang decoction decreases proteinuria, protects kidney function, and ameliorates histopathology in ADR-induced rats by preserving nephrin expression.
Shen-qi-di-huang decoction; proteinuria; nephrin; adriamycin nephropathy
Androgens have been linked to the onset, severity, and progression of rheumatoid arthritis (RA). In traditional Chinese medicine (TCM), the most common pattern in RA is kidney deficiency, which partly corresponds to a low sex hormone state. In this study, TCM kidney deficiency was induced in male Sprague-Dawley rats with castration surgery, and a TCM preparation, Yi Shen Juan Bi Pill (YJB), was used to treat collagen induced arthritis (CIA) rats with castration. Metabolomic technique was used to evaluate the pharmacological mechanism in castrated CIA rats treated by YJB. The results showed that castration significantly increased the severity of the arthritis in rats but was ameliorated by YJB. Its pharmacological mechanism was partially associated with lipid metabolites involving free fatty acid (FFA) and lysophosphatidylcholine (LPC). In conclusion, the experimental results demonstrate the protective effect of YJB on the TCM kidney deficiency pattern induced by androgen deficiency in CIA rats and support that YJB should be used for the clinical treatment of RA with TCM kidney deficiency pattern.
Emperor Shen-Nung was the second of China's mythical emperors (3500-2600 BCE). Widely considered the father of Chinese medicine, he catalogued over 365 species of medicinal plants which he personally tasted. Through his treatise ‘Shen Nung Benchau Jing’, we relive Emperor Shen-Nung's contribution to urology with reference to his management of erectile dysfunction. Time-related sources in medical and historical literature were reviewed, including the ‘Shen Nung Benchau Jing’ (The medicine book of Emperor Shen-Nung), archives and manuscripts at the Wellcome History of Medicine Collection, the Royal Society of Medicine, London, The Hong Kong Museum of Medical Sciences, and The Museum of Medical History, Shanghai, China. Chinese traditional herbal medicine began approximately 5000 years ago. Agricultural clan leader, Emperor Shen-Nung, was said to have a ‘crystal-like belly’ to watch the reactions in his own stomach of the herbs he collected. Ginseng was among of Shen Nung's contributions to herbal medicine. He experienced a warm and sexually pleasurable feeling after chewing the root. He advocated this as a treatment for erectile dysfunction and used it to stimulate sexual appetite. The reputation of ginseng as an aphrodisiac is based on the doctrine of signatures, since the adult root has a phallic shape. Shen-Nung believed that ginseng's resemblance to the human form is proof of its rejuvenative and aphrodisiac properties. It was believed that the closer the similarity to the human figure, the more potent the root. The use of ginseng for erectile dysfunction by Emperor Shen-Nung was unique for its time. It continues to hold parallels as a modern-day herbal aphrodisiac 5000 years on.
Ancient China; erectile dysfunction; ginseng; history of urology
The clinical application of Traditional Chinese medicine (TCM), using several herbs in combination (called formulas), has a history of more than one thousand years. However, the bioactive compounds that account for their therapeutic effects remain unclear. We hypothesized that the material basis of a formula are those compounds with a high content in the decoction that are maintained at a certain level in the system circulation. Network pharmacology provides new methodological insights for complicated system studies. In this study, we propose combining pharmacokinetic (PK) analysis with network pharmacology to explore the material basis of TCM formulas as exemplified by the Bushen Zhuanggu formula (BZ) composed of Psoralea corylifolia L., Aconitum carmichaeli Debx., and Cnidium monnieri (L.) Cuss. A sensitive and credible liquid chromatography tandem mass spectrometry (LC-MS/MS) method was established for the simultaneous determination of 15 compounds present in the three herbs. The concentrations of these compounds in the BZ decoction and in rat plasma after oral BZ administration were determined. Up to 12 compounds were detected in the BZ decoction, but only 5 could be analyzed using PK parameters. Combined PK results, network pharmacology analysis revealed that 4 compounds might serve as the material basis for BZ. We concluded that a sensitive, reliable, and suitable LC-MS/MS method for both the composition and pharmacokinetic study of BZ has been established. The combination of PK with network pharmacology might be a potent method for exploring the material basis of TCM formulas.
The present study was undertaken with the objective of finding out the comparative analgesic effect of Ligusticum chuanxiong (LC) pieces decoction, LC formula granule decoction, liquored LC pieces decoction and liquored LC formula granule decoction. The analgesic effects were analyzed using the hot plate and acetic-induced writhing test in mice, and antidysmenorrheic effect was observed with primary dysmenorrhea model. The results showed that four kinds of LC decoction had definite effect in delaying incubation period and decreasing the writhing frequency within 30 min. They also effectively relieved dysmenorrhea. Moreover, liquored LC had better analgesic effect than crude LC in four decoctions.
Analgesic effect; chuanxiong; dysmenorrhea test; hot plate test; writhing test
Aim of study
Coptis chinensis rhizomes (Coptidis Rhizoma, CR), also known as “Huang Lian”, is a common component of traditional Chinese herbal formulae used for the relief of abdominal pain and diarrhea. Yet, the action mechanism of CR extract in the treatment of irritable bowel syndrome is unknown. Thus, the aim of our present study is to investigate the effect of CR extract on neonatal maternal separation (NMS)-induced visceral hyperalgesia in rats and its underlying action mechanisms.
Materials and methods
Male Sprague-Dawley rats were subjected to 3-hr daily maternal separation from postnatal day 2 to day 21 to form the NMS group. The control group consists of unseparated normal (N) rats. From day 60, rats were administrated CR (0.3, 0.8 and 1.3 g/Kg) or Vehicle (Veh; 0.5% carboxymethylcellulose solution) orally for 7 days for the test and control groups, respectively.
Electromyogram (EMG) signals in response to colonic distension were measured with the NMS rats showing lower pain threshold and increased EMG activity than those of the unseparated (N) rats. CR dose-dependently increased pain threshold response and attenuated EMG activity in the NMS rats. An enzymatic immunoassay study showed that CR treatment significantly reduced the serotonin (5HT) concentration from the distal colon of NMS rats compared to the Veh (control) group. Real-time quantitative PCR and Western-blotting studies showed that CR treatment substantially reduced NMS induced cholecystokinin (CCK) expression compared with the Veh group.
These results suggest that CR extract robustly reduces visceral pain that may be mediated via the mechanism of decreasing 5HT release and CCK expression in the distal colon of rats.
cholecystokinin; Coptis chinensis rhizomes; irritable bowel syndrome; neonatal maternal separation; Ranunculaceae; serotonin
ZHENG is the key theory in traditional Chinese medicine (TCM) and it is very important to find the molecular pharmacology of traditional Chinese herbal formulae. One ZHENG is related to many diseases and the herbal formulae are aiming to ZHENG. Therefore, many herbal formulae whose effects on a certain disease have been confirmed might also treat other diseases with the same ZHENG. In this study, the microarrays collected from patients with QiXuXueYu ZHENG (Qi-deficiency and Blood-stasis syndrome) before treatment and after being treated with Fuzheng Huayu Capsule were analyzed by a high-throughput gene microarrays-based drug similarity comparison method, which could find the small molecules which had similar effects with Fuzheng Huayu Capsule. Besides getting the results of anti-inflammatory and anti-fibrosis drugs which embody the known effect of Fuzheng Huayu Capsule, many other small molecules were screened out and could reflect other types of effects of this formula in treating QiXuXueYu ZHENG, including anti-hyperglycemic, anti-hyperlipidemic, hyposenstive effect. Then we integrated this information to display the effect of Fuzheng Huayu Capsule and its potential multiple-target molecular pharmacology. Moreover, through using clinical blood-tested data to verify our prediction, Fuzheng Huayu Capsule was proved to have effects on diabetes and dyslipidemia.
The present study was undertaken to characterize the effects of Danggui-Shaoyao-San (DSS), a famous traditional Chinese medicine formula consisting of six herbal medicines, on diabetic nephropathy. Streptozotocin-induced diabetic rats were orally administrated DSS (2.8 g kg−1 per day) for 12 consecutive weeks. DSS partially decreased the high plasma glucose level in diabetic rats. Diabetic-dependent alterations in urinary albumin, 24-hour urinary albumin excretion rate, and creatinine clearance as well as the kidney hypertrophy (kidney weight/body weight ratio) and glomerular mesangial matrix expansion were ameliorated after 12 weeks of DSS treatment. The increased expression of nuclear factor-κB as well as transforming growth factor-β1 and the progressive accumulation of type IV collagen in kidney of diabetic rats were also attenuated by DSS. Not only the elevated levels of advanced glycation end products (AGEs) and Nε-(carboxymethyl)lysine but also the higher levels of lipid peroxidation products in kidney of diabetic rats were ameliorated by DSS. Decreased activity of superoxide diamutase and glutathione peroxidase in kidney of diabetic rats was enhanced by DSS. These data demonstrated that the renoprotective effects of DSS in STZ-diabetic rats not only were attributable to regulate plasma glucose to attenuate AGEs expression in diabetic glomeruli but also likely reflected its antioxidant activity.
This article exemplifies a systematic approach to revealing the complexity of Chinese herbal medicine formulae through three levels of scientific research: standardization of herbs, verification of ancient formulae and mechanism studies. We use Danggui Buxue Tang (DBT) as an example for this approach. Among thousands of traditional Chinese medicine herbal formulae, almost all of which consist of multiple herbs, DBT is one of the simplest. Containing only two herbs, namely Radix Astragali (RA) and Radix Angelicae Sinensis (RAS), DBT is traditionally used to treat ailments in women. The weight ratio of RA to RAS in DBT was prescribed to be 5:1 as early as in 1247 AD. In addition to advanced chemical analysis of herbal constituents, DNA genotyping techniques have been developed for reliable standardization of RA and RAS. Chemical evaluation shows that main active constituents in DBT, including astragaloside IV, calycosin, formononetin and ferulic acid, were most abundant after extraction at the RA to RAS ratio of 5:1, whereas other tested RA to RAS ratios only gave sub-optimal levels of the active constituents. Biological evaluation indicates that bioactivities of DBT, e.g. immuno-modulatory, oesteotropic and estrogenic effects are also best exerted at the RA to RAS ratio of 5:1. Correlation analysis demonstrates statistically significant relationship between the tested chemical constituents and tested bioactivities. Up- and down-regulation of expression of some genes as potential biomarkers has been detected by using gene chip technology. This systematic approach on the basis of herbal standardization, chemical and biological verification and mechanism studies, as exemplified in this article, will be useful to reveal the complexity of not only DBT but also other Chinese medicine herbal formulae.
Haitian migrants played an important role shaping Cuban culture and traditional ethnobotanical knowledge. An ethnobotanical investigation was conducted to collect information on medicinal plant use by Haitian immigrants and their descendants in the Province of Camagüey, Cuba.
Information was obtained from semi-structured interviews with Haitian immigrants and their descendants, direct observations, and by reviewing reports of traditional Haitian medicine in the literature.
Informants reported using 123 plant species belonging to 112 genera in 63 families. Haitian immigrants and their descendants mainly decoct or infuse aerial parts and ingest them, but medicinal baths are also relevant. Some 22 herbal mixtures are reported, including formulas for a preparation obtained using the fruit of Crescentia cujete. Cultural aspects related to traditional plant posology are addressed, as well as changes and adaptation of Haitian medicinal knowledge with emigration and integration over time.
The rapid disappearance of Haitian migrants' traditional culture due to integration and urbanization suggests that unrecorded ethnomedicinal information may be lost forever. Given this, as well as the poor availability of ethnobotanical data relating to traditional Haitian medicine, there is an urgent need to record this knowledge.