Effective Forms, Additive Effect, and Toxicities Scattering Effect of Pharmacodynamic Substances of TCMs Some Reflections Evoked by the Study on the Metabolic Disposition of Traditional Chinese Medicines (TCM) / 世界科学技术-中医药现代化

The blood concentrations of the pharmacodynamic substances of traditional Chinese medicines (TCMs) are usually very low. How can they exert pharmacological actions, in which forms (original form, metabolite or the both) do they exert the actions. To answer these questions, we proposed a new concept ofEffective Formsof pharmacodynamic substances of TCMs and a hypothesis of additive effect of multiple constituents of TCMs. The hypothesis includes that the aggregate or summation of Effective Forms of pharmacodynamic substances of TCMs is the core material base of the effi-cacy of TCMs, and the additive effect of the blood concentrations of different Effective Forms is one part of the action mechanism. The additive effect of the different Effective Forms of a TCMs means an additive effect of numerous con-stituents or/and metabolites on a same target, and therefore the efficacy brought by the addition of the concentrations of all these compounds, which different from the synergy effect of multi-constituents on multi-targets. Studies on the disposition of TCMs showed that a constituent can be biotransformed to many metabolites (up to more than 50 metabolites);different constituents can produce the same metabolites;many metabolites (up to 10 compounds for each metabolite) are isomers or homologues; some constituents can be converted to each other in vivo; and some metabolites are bioactive. These com-pounds having the similar structure are likely to have the same pharmacological effects on the same target, which could provide experimental evidences for the concept ofEffective Formsand the hypothesis ofAdditive Effect. We suggest that the Effective Forms and Additive Effects of the pharmacodynamic substances of TCMs should be extensively investi-gated in the future, and the results of such researches will help us further understand the pharmacodynamic substances and action mechanism of TCMs, and give a new explanation 'Toxicities Scattering Effect' for 'Why the toxicities of TCMs are low', and propose a new strategy for quality control of TCMs.

Assessment on anti-nociception and anti-inflammation pharmacodynamics of Asarum heterotropoides var. mandshuricum and Asarum sieboldii / 中国中药杂志

<p><b>OBJECTIVE</b>To assess the anti-nociception and anti-inflammation pharmacodynamics of Asarum heterotropoides var. mandshuricum and A. sieboldii.</p><p><b>METHOD</b>Both the writhing test and hot plate test were conducted to assess the anti-nociceptive effect of Asarum and Xylene-induced mouse ear edema was conducted to assess the anti-inflammatory effect of Asarum.</p><p><b>RESULT</b>Twelve samples of A. heterotropoides var. mandshuricum and A. sieboldii from different producing areas showed anti-nociceptive and anti-inflammatory effects. Specifically, 27% to 61% of the seven samples of A. heterotropoides var. mandshuricum showed anti-nociceptive effect and while 34% to 48% of A. sieboldi showed anti-nociceptive effect. The inflammatory inhibition rate of A. heterotropoides var. mandshuricum produced in six producing areas (38%-57%) is higher than that of A. heterotropoides var. mandshuricum produced in five producing areas (34%-48%). The same kind of Asarum produced in different areas showed significant differences. A. heterotropoides var. mandshuricum produced in Jilin province (38%-57%) showed better anti-nociceptive effect than sample produced in Heilongjiang province (34%) in writhing test. A. heterotropoides var. mandshuricum produced in Heilongjiang (43%) province showed a better anti-nociceptive effect than samples produced in Liaoning province (29%-36%) in hot plate test. A. sieboldii produced in Shaanxi province (47%-49%) showed a better anti-nociceptive effect than samples produced in Hubei province (40%) in writhing test. A. sieboldii produced in Shaanxi province (45%-59%) showed better anti-nociceptive effect than samples produced in Chongqing (40%) in hot plate test. A. heterotropoides var. mandshuricum produced in Jilin province (51%-63%) showed better anti-inflammatory effect than samples produced in Heilongjiang province (50%). In totality, the results from analysis of geoherbalism showed that famous-region A. heterotropoides var. mandshuricum and A. sieboldii had a better anti-nociception effect than Asarum produced in other producing areas, famous-region A. heterotropoides var. mandshuricum had a better effect than those produced in other producing areas in anti-inflammation. But famous-region A. sieboldii showed no obvious difference from those produced in other producing areas in anti-inflammation.</p><p><b>CONCLUSION</b>All samples of Asarum showed anti-nociceptive and anti-inflammatory effects, but with significant differences among Asarum produced in different areas, indicating the eoherbalism to some extent.</p>

Research on relationship between commercial specifications of Scutellariae Radix and chemical composition and drug quality / 中国中药杂志

<p><b>OBJECTIVE</b>To compare the chemical differences in 4 commercial specifications of Scutellaria Radix, research the affection of decayed central xylem part on the crude drug's chemical composition and provide scientific data for production, processing, sale and clinical applications of Scutellariae Radix.</p><p><b>METHOD</b>Macroscopical identification method was used for observation of different specifications of Scutellariae Radix, including Qinwang, Tiaoqin both in 1st class and 2nd class and inferior samples. HPLC fingerprint method was used to analyze chemically the decayed central xylem part and non-decayed part as well as complete sample, and the results were described by the relative peak area.</p><p><b>RESULT</b>The morphological characteristics of 4 specifications are greatly different from one another mainly in root diameters, root lengths and the proportions of decayed central xylem part in the root, and so the authors classified Qinwang and Tiaoqin in 1st class as Kuqin for all samples of them which have decayed central xylem; and classified Tiaoqin in 2nd class and the inferior samples as Ziqin, for having little decayed central xylem. The 4 specifications collected from the same producing area have similar HPLC fingerprint profile to one another, while they are different in relative peak area. The peak area ratios of aglycone to their glucuronide (baicalein/baicalin, wogonin/wogonoside, oroxylin A/oroxylin A-7-O-glucuronide) from Kuqin were significantly higher than those of Ziqin. The total area of the peaks in HPLC fingerprint chromatographs of decayed central xylem part were quite lower than that of non-decayed part, whereas peak areas of the characteristic peaks and the 3 peak area ratios of decayed central xylem were significantly higher than those of non-decayed part which could be used as characteristic parameters to distinguish Kuqin and Ziqin.</p><p><b>CONCLUSION</b>Four commercial specifications of Scutellariae Radix can be classified as Kuqin and Ziqin respectively according to morphological characteristics and the proportions of decayed central xylem part in the root. The chemical characteristics of Kuqin and Ziqin are different from each other, so it's worth clarifying the similarities and differences of Kuqin and Ziqin in future. The result in this research can be used as references for identification and quality control of Scutellariae Radix specifications, and investigation on effective components of Kuqin and Ziqin.</p>

Determination of harpagide and harpagoside in Scrophulariae Radix by HPLC-UV / 中国中药杂志

<p><b>OBJECTIVE</b>To develop a method for the determination of harpagide and harpagoside in Scrophulariae Radix (Xuanshen) by HPLC-UV under double wavelength, and to study the changes of these two constituents during processing, and to set the limitation of harpagide and harpagoside contents in crude drug and sliced pieces of Xuanshen.</p><p><b>METHOD</b>The analyses were performed on an Agilent Technologies ZORBAX SB-C18 (4.6 mm x 250 mm, 5 microm) eluted with acetonitrile-water (containing 0.03% phosphoric acid) in gradient model. The flow rate was 1.0 mL x min(-1) . The column temperature was 25 degrees C. The UV detector wavelength was set at 210 nm before 13 min and then changed to 280 nm.</p><p><b>RESULT</b>Harpagide and harpagoside were separated well. The linear calibration curves were obtained over of 0.0549 - 1.46 microg for harpagide (r = 0.9999, n =7) ,0.0225 - 0.900 microg for harpagoside (r = 0.9998, n = 9). The recoveries ( +/- RSD)% were 98.1 (+/- 2.4)% for harpagide and 98.8 (+/- 4.3)% for harpagoside. The contents of harpagide were 0. 277% - 0.620%, harpagoside were 0.078% - 0.362% in Xuanshen, and harpagide were 0.276% - 1.059%, harpagoside were 0. 059% - 0.183% in sliced Xuanshen, respectively. After the processing of Scrophulariae Radix, the content of harpagide increases 13.7% - 96.0%, while harpagoside decreases 11.0%-73.9%.</p><p><b>CONCLUSION</b>This method is simple, accurate, and can be used for the quality control of Scrophulariae Radix. We propose that the total content of harpagide and harpagoside in either crude drug or sliced pieces of Scrophulariae Radix should not be less than 0.45%.</p>

Chemical constituent from fruit of Aristolochia contorta / 中国中药杂志

<p><b>OBJECTIVE</b>To study the chemical constituents of the fruit of Aristolochia contorta.</p><p><b>METHOD</b>The compounds were isolated by chromatographic techniques and crystalization, the structures were elucidated by spectrum analysis.</p><p><b>RESULT</b>Fifteen compounds were isolated from the dry fruit of A. contorta, which were six aristolochic acids: aristolochic acid I, aristolochic acid III a, aristolochic acid IVa, aristolochic acid II, aristolochic acid III and aristolochic acid VIIa. Three aristolactams: aristololactam I, aristololactam II and aristololactam IIIa. Three phenolic acids syringic acid, vanillic acid and p-coumaric acid. Three other type compounds: pentacosane acid, beta-sitosterol and daucossterol.</p><p><b>CONCLUSION</b>Aristolochic acid III, aristolochic acid VIIa, aristololactam IIIa, and penfacosane acid were isolated from A. contorta for the first time, and compounds 4-13 were isolated from the furit of A. contorta for the first time.</p>

Screening effective parts of combination of Astragali Radix and Angelicae Sinensis Radix (A&A) for its renoprotective effects / 中国中药杂志

<p><b>OBJECTIVE</b>The decoction of Astragali Radix and Angelicae Sinensis Radix (A&A) has shown antifibrotic effects in rats with unilateral ureteral obstruction (UUO). The aim of this study was to track the effective parts of A&A for its renoprotective effects, according to the improvement of renal function and renal tubulointerstitial damage.</p><p><b>METHOD</b>A&A was sequentially extracted by using different solvents for three times and eleven different parts were gained. Wistar rats were randomly divided into Sham, UUO and the treatment groups with A&A or each part of A&A. After administration of A&A or its parts for 10 days, the levels of serum creatinin (Scr) and urea were measured. The morphological changes of kidneys were also semi-quantitatively analyzed by HE, Masson stained tissue sections, which including interstitial cell infiltration, tubular atrophy and interstitial fibrosis.</p><p><b>RESULT</b>The levels of Scr, urea were significantly increased, accompanied with severe renal damage in rats with UUO. As same as A&A, the part I in the first extraction and part IC in the second extraction were all shown to decrease the levels of Scr and urea and the index of renal interstitial damage. However, the following 4 parts extracted from IC in the third extraction were shown no effect on the above indexes.</p><p><b>CONCLUSION</b>The extract part I and part IC could be considered as the predominant parts of A&A for its renoprotective effects, due to their improvement of renal damage in interstitial nephropathy.</p>

Surveys on resources and varieties on Chinese markets of crude drug Xixin / 中国中药杂志

Many species of the genus Asarum plants are used as Chinese traditional or folk medicines, in Chinese which are known as "Xixin" (Asari Radix et Rhizoma) , "Bei-Xixin" , "Hua-Xixin" and "Nan-Xixin" , etc. In order to get a clear picture of resources distribution and varieties on Chinese markets of the crude drug Xixin and provide scientific basis for their resource conservation and sustainable use, during recent years we conducted field investigations and market researches many times. The results showed that the resources of both official Xixins and non-official Xixins were decreased because of the ecological environment damage and over-digging, especially species whose population size was small. Bei-Xixin derived from A. heterotropoides var. mandshuricum was the most species on the Chinese markets except for a few areas of China. Hua-Xixin derived from A. sieboldii and non-official Xixins were mainly used in their producing areas. Cultivation of Hua-Xixin should be greatly developed, and wild resources of non-official species must be preserved strictly.

Anti-inflammatory and anti-nociceptive effects in mice of water and ethanol extracts of roots and rhizomes of Asarum heterotropoides var. mandshuricum / 中国中药杂志

<p><b>OBJECTIVE</b>To compare the anti-inflammatory and anti-nociceptive effects of the different water extracts which were prepared by regular decoction time or removing volatie oil and ethanol extracts which were prepared in different concentration ethanol of Xixin (the roots and rhizomes of Asarum heterotropoides var. mandshuricum), and then to investigate the anti-inflammatory and antinociceptive mechanisms.</p><p><b>METHOD</b>Xylene-induced ICR mouse ear edema and hot plate test were utilized to evaluate the anti-inflammatory and anti-nociceptive effects of Xixin at different dose level (water extracts of regular decoction time or removing volatie oil at the dose of 0.8 g x kg(-1) and 1.6 g x kg(-1); 95% ethanol extracts at the dose of 0.91 g x kg(-1) and 1.82 g x kg(-1); 50% ethanol extracts at the dose of 0.76 g x kg(-1) and 1.52 g x kg(-1)). Xylene-induced adrenalectomized mouse ear edema model was used to study the anti-inflammatory mechanisms. To reveal the anti-nociceptive mechanisms, mice were pretreated with naloxone in the hot plate test.</p><p><b>RESULT</b>The water extracts significantly reduced the weight of ear edema as compared with control group. Inhibition ratios were 43.20% and 63.69% at the higher dose, respectively. The ethanol extracts also significantly reduced the weight of ear edema and the inhibition ratios were 61.86% and 52. 56% at the higher dose, respectively. Mice administered water extracts delayed the latency times in the hot plate test. The anti-nociceptive effects of water extracts peaked at 2.0 h after i.g. administration. The hot plate latency times were increased by 51.27%, 62.78%, 60.08% and 68.00% at peak time, respectively. Regular decoction time group showed more significant effects in both models. The anti-inflammatory effect of 95% ethanol extracts was similar to 50% ethanol extracts. The water extracts were not effective in reducing xylene-induced adrenalectomized mouse ear edema. The anti-nociceptive effect of water extracts was blocked by naloxone.</p><p><b>CONCLUSION</b>Both the water extracts and ethanol extracts of Xixin showed considerable anti-inflammatory potency against xylene induced inflammation. The water extracts produced anti-nociception in thermal model. The water extracts prepared in regular decoction time showed better anti-inflammatory and anti-nociceptive effects. Both the 95% ethanol and 50% ethanol extracts showed similarly anti-inflammatory effects. The anti-inflammatory effect of water extracts related to adrenal gland. The anti-nociceptive effect of water extracts was involved in activating opioid receptor.</p>

Study on preparation and quantity determination of Scrophularia ningpoensis dispensing granules / 中国中药杂志

<p><b>OBJECTIVE</b>To develop the preparation method and to determine the quantity of effective constituents of Scrophularia ningpoensis dispensing granules.</p><p><b>METHOD</b>Nine experiments were carried out through L9 (3(4)) orthogonal design. The contents of harpagoside and cinnamic acid were determined by HPLC method.</p><p><b>RESULT</b>The optimal extraction process was as follows: the slices were soaked in water in the ratio of 1:8 for 0.5 h, then they were decocted for 2 h. For the second time, 6 times of water was added and sustained for 1.5 h. Harpagoside and cinnamic acid were linear within the ranges of 0.0776-1.552 microg (r=0.9999) and 0.01446-0.4339 microg (r=0.9999), respectively. The average recoveries were 100.4% (RSD 1.98%, n=6) and 98.27% (RSD1.35%, n=6), respectively. Ten batches of granules were determined.</p><p><b>CONCLUSION</b>The extraction process is scientific and the determination method is suitable for quality control of Scrophularia ningpoensis dispensing granules.</p>

Study on pharmacodynamics of Chinese herbal drug Guijiu and its lignan / 中草药

Object To study the antitumor effects of extracts from the fruits, roots and rhizomes of Sinopodophyllum emodi (Wall.) Ying, the roots and rhizomes of Dysosma furfuracea S.Y. Bao and the podophyllotoxin, deoxypodophyllotoxin of Guijiu plants in mice. Methods Tumor borne mice with transplanted HepA and Ehrlich ascites carcinoma (EAC) were used to observe the antitumor and the liver protective effects of the above five samples, which were given orally. Results Extracts of roots and rhizomes of S. emodi, and D. furfuracea showed the significant antitumor effects. Conclusion All the five samples have antitumor activity.