Medical benefits of using natural compounds and their derivatives having multiple pharmacological actions.
The multiple pharmacological actions of a unique compound are a prerequisite for classifying drugs as highly efficacious, because the multiple pharmacological actions offer the possibility of treating various symptoms of chronic diseases as described below. 1) Sustained hyperglycemia induces macrovascular and microvascular complications in type 2 diabetes mellitus. Antihyperglycemic medication and the control of postprandial hyperglycemia are essentially important for normalizing plasma glucose level. Gymnemic acid IV isolated from Gymnema sylvestre (Asclepiadaceae) leaves has antisweet, antihyperglycemic, glucose uptake inhibitory, and gut glycosidase inhibitory effects. Most of these pharmacological effects may synergistically contribute to alleviating type 2 diabetes-related symptoms. 2) Diabetic skeletal and vascular smooth muscles are hypersensitive to chemical transmitters, cytokines and autacoids. The sensitivity of neuromuscular synapses is enhanced in diabetes, which seems to be closely associated with neuropathy as one of the diabetic complications. beta-Eudesmol found in Atractylodes lancea rhizome has a desensitizing channel blocking action to nicotinic acetylcholine receptors, anti-angiogenic action in vascular endothelium, and neuronal differentiation actions. These multiple pharmacological actions are favorable for treating angiogenic diseases possibly including the complications of diabetes, namely, retinopathy and nephropathy, and cancer. 3) Nipradilol is clinically utilized as a topical antiglaucoma drug. The ocular hypotensive effects of this compound are brought about by its alpha1 and beta-adrenergic receptor blocking actions, and nitric oxide (NO) releasing action. NO directly activates cyclooxygenases. All these pharmacologic effects are beneficial for treating glaucoma. The selectivity and specificity of drug action are required for treating acute diseases, infections or for acting as useful reagents. The pleiotropic actions of natural compounds and their derivatives serve as important clues for developing new drugs for various chronic diseases. (+info)
Analysis of the sesquiterpenoids in processed Atractylodis Rhizoma.
In Asia, processed Atractylodis Rhizoma, the dried rhizome of Atractylodes ovata De Candolle (Compositae), is widely used as a tonic agent in herbal diets; stir-frying with soil is the most common processing method. In this study, we focused on determining variations in the function and concentrations of sesquiterpenoids in processed Atractylodis Rhizoma. Raw Atractylodis Rhizoma was processed by stir-frying it with different assistant substrates (i.e., red soil and burnt clay). The results indicated that there was less atractylon in stir-fried materials than in raw materials. However, there were higher levels of atractylenolides II and III in stir-fried materials than in raw materials. We also found that the heavy-metal content in burnt clay exceeded regulations set by the Taiwanese government. Moreover, commercial Atractylodis Rhizoma in Taiwan exhibited great differences in concentrations of the active components. In addition, atractylon showed stronger cytotoxicity than atractylenolides II and III in various cell lines. Therefore, we suggest that the toxic effects of atractylon are reduced following atractylon degradation to atractylenolides II and III. In conclusion, the toxicity of Atractylodis Rhizoma is reduced through processing. (+info)
Inhibition of melanogenesis by selina-4(14),7(11)-dien-8-one isolated from Atractylodis Rhizoma Alba.
To develop effective skin-lightening agents, we tested medicinal herbal extracts for their melanogenic-inhibitory activities. We isolated a sesquiterpenoid compound from the extract of Atractylodis Rhizoma Alba using the bioactivity-guided fractionation and identified it as selina-4(14),7(11)-dien-8-one (compound 1) with spectroscopic methods. Compound 1 dramatically reduced melanin synthesis of melan-a cells without any apparent cytotoxicity. Compound 1 did not inhibit cell-free tyrosinase activity but decreased tyrosinase activity in melanocytes. These effects were attributed to reduced expression of melanogenic enzymes such as tyrosinase, tyrosinase-related protein 1 (TRP-1), and tyrosinase-related protein 2 (TRP-2). These results suggest that compound 1 may be an effective skin-lightening agent that regulates expression of melanogenic enzymes. (+info)
Effects of Wei Chang An on expression of multiple genes in human gastric cancer grafted onto nude mice.
AIM: To investigate the expression of multiple genes in Chinese jianpi herbal recipe Wei Chang An (WCA) in human gastric cancer cell line SGC-7901. METHODS: A human gastric adenocarcinoma cell line SGC-7901 grafted onto nude mice was used as the animal model. The mice were randomly divided into 3 groups, one control and the two representing experimental conditions. Animals in the two experimental groups received either WCA over a 34-d period or 5-fluorouracil (5-FU) over 6-d period starting at 8th d after grafting. Control animals received saline on an identical schedule. Animals were killed 41 d after being grafted. The expression profiles in paired WCA treated gastric cancer samples and the N.S. control samples were studied by using a cDNA array representing 14181 cDNA clusters. The alterations in gene expression levels were confirmed by Real-time Quantitative polymerase chain reaction (qPCR). RESULTS: When compared with controls, the average tumor inhibitory rate in WCA group was 44.32% +/- 5.67% and 5-FU 47.04% +/- 11.33% (P < 0.01, respectively). The average labeling index (LI) for PCNA in WCA group and 5-FU group was significantly decreased compared with the control group. Apoptotic index (AI) was significantly increased to 9.72% +/- 4.51% using the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate fluorescence nick end labeling (TUNEL) method in WCA group compared with the controls 2.45% +/- 1.37%. 5-FU group was also found to have a significantly increased AI compared with the controls. The expression of cleaved Caspase-3 in WCA group and 5-FU group was significantly increased compared with the control group respectively. There were 45 different expressed sequence tags (ESTs) among the control sample pool and WCA sample pool. There were 24 ESTs up-regulated in WCA samples and 21 ESTs down-regulated. By using qPCR, the expression level of Stat3, rap2 interacting protein x (RIPX), regulator of differentiation 1 (ROD1) and Bcl-2 was lower in WCA group than that in control group respectively. By using SP immunohistochemical method the expression of Phospho-Stat3 (Tyr705) and Bcl-2 in WCA group and 5-FU group was significantly decreased compared with the control group respectively. CONCLUSION: WCA could inhibit gastric cancer cell SGC-7901 growth in vivo. WCA could induce gastric cancer cell apoptosis and suppress proliferation. Its mechanisms might be involved in the down-regulation of Stat3, RIPX, ROD1 and Bcl-2 gene. (+info)
Inhibitory effects of Atractylodis lanceae rhizoma and Poria on collagen- or thromboxane A2-induced aggregation in rabbit platelets.
Kami-shoyo-san (Jia-Wei-Xiao-Yao-San), Toki-shakuyaku-san (Dang-Gui-Shao-Yao-San) and Toki-shigyaku-ka-goshuyu-shokyo-to (Dang-Gui-Si-Ni-Jia-Wu-Zhu-Yu-Sheng-Jiang-Tang) are Kampo (traditional Chinese) medicines which are traditionally and effectively used for the treatment of chilly sensation (Hiesho) in Japan, but the active components and their detailed mechanisms have not yet been clarified. Etiologies of Hiesho include poor peripheral blood circulation and platelet aggregability contributes to peripheral blood circulation; therefore, we investigated the effect of Kampo medicines on platelet aggregation using rabbit platelets in vitro. Collagen and U46619, a thromboxane A(2) receptor agonist, caused rabbit platelet aggregation, which was potently inhibited by pretreatment of platelets with Kami-shoyo-san and Toki-shakuyaku-san in vitro. Toki-shigyaku-ka-goshuyu-shokyo-to, however, did not significantly inhibit collagen- or U46619-induced platelet aggregation. Therefore, we examined the effect on platelet aggregation of two herbal medicines, Atractylodis Lanceae Rhizoma and Poria, both of which are contained in Kami-shoyo-san and Toki-shakuyaku-san but not in Toki-shigyaku-ka-goshuyu-shokyo-to. As the results indicate, Atractylodis Lanceae Rhizoma inhibited platelet aggregation induced by collagen but not by U46619. Poria effectively inhibited U46619-induced platelet aggregation and it partially inhibited collagen-induced platelet aggregation. On the other hand, Atractylodis Lanceae Rhizoma and Poria did not inhibit adrenaline/adenosine diphosphate- or adrenaline/serotonin-induced platelet aggregation. These results suggest the possibility that the inhibition of platelet aggregation by two Kampo medicines, Kami-shoyo-san and Toki-shakuyaku-san, is one of the mechanisms underlying the improvement of Hiesho. Furthermore, Atractylodis Lanceae Rhizoma and Poria are possible herbal medicines for the inhibition of platelet aggregation. (+info)
Biotransformation of a herb plant metabolite by a cell disruptant of Chlamydomonas reinhardtii.
Atractylenolide III is an organic product of the herb plant Atractylodes ovata that is used as an anti-inflammatory. This compound has very limited solubility in water, but we succeeded in transforming it using a Chlamydomonas cell disruptant containing 9.1% dimethyl sulfoxide. Two types of metabolites were confirmed after 3 h of incubation by gas chromatography, besides the non-modified substrate. Nuclear magnetic resonance and gas chromatography-mass spectrometry analyses indicated that one of the metabolites had two hydroxyl groups whereas atractylenolide III had one hydroxyl group, but no metabolite was obtained when atractylenolide III was added directly to the Chlamydomonas culture medium for 10 d. (+info)
Cytotoxic activity of Thai medicinal plants against human cholangiocarcinoma, laryngeal and hepatocarcinoma cells in vitro.