A Chinese Herbal Decoction, Shaoyao-Gancao Tang, Exerts Analgesic Effect by Down-Regulating the TRPV1 Channel in a Rat Model of Arthritic Pain.

Shaoyao-Gancao Tang (SGT) is one of the most frequently used compound formulas in the treatment of pain-related diseases in the medical practice of traditional Chinese medicine (TCM). To investigate the anti-inflammatory and antinociceptive effects, as well as to uncover the molecular mechanism of SGT, the rat pain model of arthritis was experimentally induced by single unilateral injection of rats' left hind paw with Freund's complete adjuvant (FCA). SGT was orally administered to the rats daily at three doses individually for a period of 16 days post-model induction. Swollen degrees and pain thresholds of the rats in different groups were measured for evaluation of the anti-inflammatory and anti-nociceptive effects of SGT. Furthermore, the mRNA and protein expression levels of transient receptor potential ion channel protein vanilloid receptor 1 (TRPV1) channel as well as its calcium-mediating function in the isolated DRG neurons were further detected to provide indexes for exploration of the molecular mechanisms mediating anti-arthritic activities of SGT. As a result, FCA injection induced significant allodynia, inflammation and edema, accompanied by a significant increase in both expression and calcium-mediating function of the TRPV1 channel. Pharmacologically, oral administration of SGT at a high or middle dose demonstrated a significant relief from the above-mentioned pathological conditions in a dose-dependent manner. Simultaneously the mRNA and protein expressional levels of TRPV1 channel, as well as its calcium-mediating function, were down-regulated greatly. These findings suggest that SGT possesses a significant analgesic and anti-inflammatory effect on arthritis rats; its therapeutic activities might be achieved through reversing the elevated expression and function of TRPV1 channel evoked by FCA.

Antitumor activities of biscoumarin and dihydropyran derivatives.

Rising worldwide cancer incidence and resistance to current anti-cancer drugs necessitate the need for new pharmaceutical compounds and drug delivery system. Two novel series of biscoumarin (1-4) and dihydropyran (5-16) derivatives were synthesized via a one-pot multicomponent condensation reaction and evaluated for their antitumor activity in vitro. The X-ray crystal structure analysis of four representative compounds 2, 7, 10 and 13 confirmed the structures of these compounds. Compounds 1-4 showed the most potent antitumor activity among the total 16 derivatives. More interestingly, preliminary mechanism studies revealed that the most potent compound 4 induced apoptosis and arrested the cell cycle at the S phase in HUTU80 cells. Additionally, the increased accumulation of HUTU80 cells in the sub G1 peak further pointed to the occurence of the cell apoptosis. The selectivity index analysis demonstrated that all the biscoumarin compounds (SI=3.1-7.5) possess higher selectivity towards intestinal epithelial adenocarcinoma cell line (HuTu80) than positive control drug carboplatin (SI=1.6-1.8). The biscoumarin compounds also showed no obvious acute toxicity on mice.

The rhizome of Gastrodia elata Blume - An ethnopharmacological review.

ETHNOPHARMACOLOGICAL RELEVANCE: Gastrodia elata Blume (Orchidaceae) is commonly called Tian ma in Chinese and mainly distributed in the mountainous areas of eastern Asia, such as China, Korea, Japan and India. It is an extensively used traditional Chinese herbal medicine in the clinical practice of traditional Chinese medicine, to treat headache, migraine, dizziness, epilepsy, infantile convulsion, tetany and so on. The present paper reviews the advancements in investigation of botany and ethnopharmacology, phytochemistry, pharmacology, toxicology and quality control of Gastrodia elata Blume. Finally, the possible tendency and perspective for future investigation of this plant are also put forward. MATERIALS AND METHODS: The information on Gastrodia elata Blume was collected via piles of resources including classic books about Chinese herbal medicine, and scientific databases including Pubmed, Google Scholar, ACS, Web of science, ScienceDirect databases, CNKI and others. Plant taxonomy was validated by the databases "The Plant List", and "Mansfeld's Encyclopedia". RESULTS: Over 81 compounds from this plant have been isolated and identified, phenolics and polysaccharides are generally considered as the characteristic and active constituents of Gastrodia elata Blume. Its active compounds possess wide-reaching biological activities, including sedative, hypnotic, antiepileptic, anticonvulsive, antianxietic, antidepressant, neuroprotective, antipsychotic, anti-vertigo, circulatory system modulating, anti-inflammationary, analgesic, antioxidative, memory-improving and antiaging, antivirus and antitumor effects. CONCLUSION: Despite the publication of various papers on Gastrodia elata Blume, there is still, however, the need for definitive research and clarification of other bioactive compounds using bioactivity-guided isolation strategies, and the possible mechanism of action as well as potential synergistic or antagonistic effects of multi-component mixtures derived from Gastrodia elata Blume need to be evaluated. It is also necessary and important to do more quality control and toxicological study on human subjects in order to maintain its efficacy stable in the body and validate its safety in clinical uses. In addition, more investigations on other parts of this plant beyond the tubers are needed. Further studies on Gastrodia elata Blume will lead to the development of new drugs and therapeutics for various diseases, and how to utilize it better should be paid more attention to.

Synthesis of biscoumarin and dihydropyran derivatives with promising antitumor and antibacterial activities.

Two series of biscoumarin (1-3) and dihydropyran (4-12) derivatives were successfully synthesized as new antitumor and antibacterial agents. The molecular structures of four representative compounds 2, 4, 7 and 10 were confirmed by single crystal X-ray diffraction study. The synthesized compounds (1-12) were evaluated for their antitumor activities against human intestinal epithelial adenocarcinoma cell line (HuTu80), mammary adenocarcinoma cell line (4T1) and pancreatic cancer cell line (PANC1) and antibacterial activities against one drug-sensitive Staphylococcus aureus (S. aureus ATCC 29213) strain and three MRSA strains (MRSA XJ 75302, Mu50, USA 300 LAC). The further mechanism study demonstrated that the most potent compound 1 could obviously inhibit the proliferation of cancer cells via the mechanism to induce apoptosis.

Antibacterial and Antitumor Activities of Biscoumarin and Dihydropyran Derivatives.

A novel series of biscoumarin (1-4) and dihydropyran (5-13) derivatives were synthesized via a one-pot multicomponent condensation reaction and evaluated for antibacterial and antitumor activity in vitro. The X-ray crystal structure analysis of four representative compounds, 3, 7, 9 and 11, confirmed the structures of these compounds. Compounds 1-4 showed the most potent antitumor activity among the total 13 derivatives; especially for compounds 1 and 2, they also emerged as promising antibacterial members with better antibacterial activity. In addition, the results of density functional theory (DFT) showed that compared with compounds 3 and 4, biscoumarins 1 and 2 had lower intramolecular hydrogen bonds (HB) energy in their structures.

[Essence of professor SHI Xin-de's experience in application of persicae ramulus-associated prescriptions].

Persicae Ramulus decoction, as the first prescription in Treatise on febrile Diseases, has been recommended by physicians of successive generations. It is also the general prescription for harmonizing yingfen and weifen, yin and yang, qi and blood. Although it only consists of five herbal medicines, it has a wider range of application and more categorized formulas than other prescriptions. Though Persicae Ramulus decoction was originally formulated to treat taiyang apoplexy, it has functions beyond the treatment of exopathic diseases. This formula is also effective in treating internal diseases, surgical diseases, gynecologic diseases, paediatric diseases, etc. KE Yun-bo praised it as the No. 1 formula among ZHANG Zhong-jin's formulas as well as the general prescription for harmonizing Yin and Yang, yingfen and weifen, resolving fleshy exterior and inducing perspiration. Professor SHI Xin-de has been expert at treating intractable diseases by using Persicae Ramulus-associated prescriptions, such as Xiaojianzhong decoction and Baohe pill for children's chronic eczema, Persicae Ramulus and Puerariae Lobatae Radix decoction and Yupingfeng powder for chronic nephritis, and Persicae Ramulus and Longgu Muli decoction for insomnia. Instead of being restricted to Chinese or Western disease names, he prescribed appropriate formulas according to syndromes, thereby achieving a good efficacy.

Reciprocal effects of Guizhi decoction to the Guizhi decoction syndrome by toll-like receptor mRNA expression and cytokines secretion.

OBJECTIVE: To explore the pathological mechanisms of Guizhi Decoction () syndrome and the therapeutic molecular mechanisms of the Guizhi Decoction, Mahuang Decoction (), Sangju Decoction ( ) and Yinqiao Powder (), as well as the potentially biological basis that Guizhi Decoction is most effective only for the patients with Guizhi Decoction syndrome in clinical practice. METHODS: We first got serum samples from the patients suffering from both upper respiratory tract infection and Guizhi Decoction syndrome identified by the doctors of Chinese medicine (CM) in the clinic. Four formulas with therapeutic actions of pungent warmth or pungent coolness for superficial syndromes were chosen and four kinds of rat serum samples each containing one of the above-mentioned herbal formulas were collected, then the effects of Guizhi Decoction syndromes' patient serum as well as the effects of sera containing the formulas after being stimulated by the patient serum samples on both the mRNA expression of certain toll-like receptor (TLR) subtypes and the release of some inflammatory cytokines in RAW264.7 cells were tested and analyzed in vitro. RESULTS: The expression of TLR-3, TLR-4 and TLR-9 mRNA among the 9 tested TLR subforms were up-regulated in the macrophages stimulated by the sera from untreated upper respiratory infection patients with the Guizhi Decoction syndrome (symptomcomplex). The products such as interleukin (IL)-1ß, IL-6, tumor necrosis factor (TNF)-α and interferon (IFN)-ß from stimulated macrophages through TLR signaling pathways were also increased correspondingly. Interestingly, the changes induced by the Guizhi Decoction syndrome patients' sera were masked significantly after the macrophages were incubated with the sera from donors treated with Guizhi Decoction. Similarly, the three other exterior-releasing formulas were all effective in reversing the up-regulated changes of certain TLR subforms to different degrees, but both the number of targeted TLRs and efficacy of them seemed to be inferior to that of Guizhi Decoction. CONCLUSION: Evidence from these experiments might contribute to the scientific explanation of both the pharmacological mechanisms of Guizhi Decoction and also the CM theory that Guizhi Decoction is specifically prescribed for the treatment of Guizhi Decoction syndrome (The gearing formula to the symptom-complex).

Zhen gan xi feng decoction, a traditional chinese herbal formula, for the treatment of essential hypertension: a systematic review of randomized controlled trials.

Objectives. To assess the clinical effectiveness and adverse effects of Zhen Gan Xi Feng Decoction (ZGXFD) for essential hypertension (EH). Methods. Five major electronic databases were searched up to August 2012 to retrieve any potential randomized controlled trials designed to evaluate the clinical effectiveness of ZGXFD for EH reported in any language, with main outcome measure as blood pressure (BP). Results. Six randomized trials were included. Methodological quality of the trials was evaluated as generally low. Four trials compared prescriptions based on ZGXFD with antihypertensive drugs. Meta-analysis showed that ZGXFD was more effective in BP control and TCM syndrome and symptom differentiation (TCM-SSD) scores than antihypertensive drugs. Two trials compared the combination of modified ZGXFD plus antihypertensive drugs with antihypertensive drugs. Meta-analysis showed that there is significant beneficial effect on TCM-SSD scores. However, no significant effect on BP was found. The safety of ZGXFD is still uncertain. Conclusions. ZGXFD appears to be effective in improving blood pressure and hypertension-related symptoms for EH. However, the evidence remains weak due to poor methodological quality of the included studies. More rigorous trials are warranted to support their clinical use.

Chinese patent medicine liu wei di huang wan combined with antihypertensive drugs, a new integrative medicine therapy, for the treatment of essential hypertension: a systematic review of randomized controlled trials.

Objectives. To assess the beneficial and adverse effects of Liu Wei Di Huang Wan (LWDHW), combined with antihypertensive drugs, for essential hypertension. Methods. Five major electronic databases were searched up to August 2012 to retrieve any potential randomized controlled trials designed to evaluate the clinical effectiveness of LWDHW combined with antihypertensive drugs for essential hypertension reported in any language, with main outcome measures as blood pressure. The quality of the included studies was assessed with the Jadad scale and a customized standard quality assessment scale. Results. 6 randomized trials were included. The methodological quality of the trials was evaluated as generally low. The pooled results showed that LWDHW combined with antihypertensive drugs was more effective in blood pressure and the scale for TCM syndrome and symptom differentiation scores compared with antihypertensive drugs alone. Most of the trials did not report adverse events, and the safety is still uncertain. Conclusions. LWDHW combined with antihypertensive drugs appears to be effective in improving blood pressure and symptoms in patients with essential hypertension. However, the evidence remains weak due to the poor methodological quality of the included studies.

Banxia baizhu tianma decoction for essential hypertension: a systematic review of randomized controlled trials.

Objectives. To assess the current clinical evidence of Banxia Baizhu Tianma Decoction (BBTD) for essential hypertension (EH). Search Strategy. Electronic databases were searched until July 2012. Inclusion Criteria. We included randomized clinical trials testing BBTD against placebo, antihypertensive drugs, or combined with antihypertensive drugs against antihypertensive drugs. Data Extraction and Analyses. Study selection, data extraction, quality assessment, and data analyses were conducted according to Cochrane standards. Results. 16 randomized trials were included. Methodological quality of the included trials was evaluated as generally low. 2 trials compared prescriptions based on BBTD using alone with antihypertensive drugs. Meta-analysis showed no significant effect of modified BBTD compared with captopril in systolic blood pressure (MD: -0.75 (-5.77, 4.27); P = 0.77) and diastolic blood pressure (MD: -0.75 (-2.89, 1.39); P = 0.49). 14 trials compared the combination of BBTD or modified BBTD plus antihypertensive drugs with antihypertensive drugs. Meta-analysis showed there are significant beneficial effect on systolic blood pressure in the combination group compare to the antihypertensive drugs (MD: -4.33 (-8.44, -0.22); P = 0.04). The safety of BBTD is uncertain. Conclusions. There is encouraging evidence of BBTD for lowering SBP, but evidence remains weak. Rigorously designed trials are warranted to confirm these results.

[Effects of ingredients from Chinese herbs with nature of cold or hot on expression of TRPV1 and TRPM8].

OBJECTIVE: To study the effects of the ingredients from Chinese herbs with the nature of cold or hot on the expression of TRPV1 and TRPM8. METHOD: The effects of ingredients from herbs on primary culture DRG neurons are observed in vitro. The expression quantity of gene is detected by the method of real time PCR. the 2 (-deltadeltaCT) method is applied to analyze the data. RESULT: Ingredients from herbs with the nature of cold up-regulate the expression level of TRPV1 and down-regulate that of TRPM8, especially under the temperature condition of 39 degrees C; while ingredients from herbs with the nature of hot up-regulate the expression level of TRPM8 and down-regulated that of TRPV1, which is more significant under the temperature condition of 19 degrees C. CONCLUSION: The regulatory changes of TRPV1 and TRPM8 mRNA expression induced by the chemical ingredients might be related to the cold and hot natures of the herbs from which the ingredients are extracted. And this could be one of the therapeutic mechanisms for the treatment of Chinese herbal medicines to cold- and heat-related diseases.

Emodin down-regulates expression of TRPV1 mRNA and its function in DRG neurons in vitro.

Emodin is a principle ingredient isolated from rhubarb rhizome, which is commonly used for constipation or pain-related diseases in traditional Chinese medicine (TCM) practice. The transient receptor potential vanilloid 1 ion channel proteins (TRPV1) are abundantly expressed in the peripheral sensory neurons and are assumed to act as a kind of nociceptor involved in the perception of pain and development of hyperalgesia. The aim of this study was to further unravel the analgesic mechanisms of rhubarb through investigating the effects of its main constitutive ingredient emodin on the expression of TRPV1 mRNA as well as on its calcium- mediating functions in vitro. The primary DRG neurons with a high purity and viability were obtained, and the TRPV1 mRNA expression levels were examined by using real-time RT-PCR and the elevated amplitudes of intracellular [Ca(2+)]i in the DRG neurons evoked by TRPV1 agonist capsaicin were examined by confocal microscopy. The results showed that emodin could significantly down-regulate both the mRNA expression of TRPV1 and the capsaicin-evoked intracellular fluorescent intensity in the DRG neurons under both 37 degrees C and 39 degrees C in vitro. Concomitantly, all of the changes induced by emodin could not be blocked by pretreatment of the primary neurons with capsazepine, an antagonist of TRPV1. In conclusion, we established that the mRNA expression level of TRPV1 and its calcium-mediating function in naive DRG neurons could be down-regulated by emodin through perhaps the non-TRPV1 channel pathways, and this might be the molecular mechanisms for rhubarb to inhibit hyperalgesia induced by inflammatory stimuli.

Cinnamaldehyde up-regulates the mRNA expression level of TRPV1 receptor potential ion channel protein and its function in primary rat DRG neurons in vitro.

Cinnamaldehyde (1) is a pharmacologically active ingredient isolated from cassia twig (Ramulus Cinnamomi), which is commonly used in herbal remedies to treat fever-related diseases. Both TRPV1 and TRPM8 ion channel proteins are abundantly expressed in sensory neurons, and are assumed to act as a thermosensor, with the former mediating the feeling of warmth and the latter the feeling of cold in the body. Both of them have recently been reported to be involved in thermoregulation. The purpose of this paper is to further uncover the antipyretic mechanisms of 1 by investigating its effects on the mRNA expression levels and functions of both TRPV1 and TRPM8. The results showed that 1 could up-regulate the mRNA expression levels of TRPV1 at both 37 and 39 degrees C, and its calcium-mediating function was significantly increased at 39 degrees C, all of which could not be blocked by pretreatment of the neuronal cells with ruthenium red, a general transient receptor potential (TRP) blocker, indicating that the action of 1 was achieved through a non-TRPA1 channel pathway. In conclusion, the findings in our in vitro studies might account for part of the peripheral molecular mechanisms for the antipyretic action of 1.