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1.
China Journal of Chinese Materia Medica ; (24): 6294-6306, 2023.
Article in Chinese | WPRIM | ID: wpr-1008828

ABSTRACT

Excessive and persistent inflammatory responses are a potential pathological condition that can lead to diseases of various systems, including nervous, respiratory, digestive, circulatory, and endocrine systems. Cannabinoid type 2 receptor(CB2R) belongs to the G protein-coupled receptor family and is widely distributed in immune cells, peripheral tissues, and the central nervous system. It plays a role in inflammatory responses under various pathological conditions. The down-regulation of CB2R activity is an important marker of inflammation and and CB2R modulators have been shown to have anti-inflammatory effects. This study explored the relationship between CB2R and inflammatory responses, delved into its regulatory mechanisms in inflammatory diseases, and summarized the research progress on CB2R modulators from plants other than cannabis, including plant extracts and monomeric compounds, in exerting anti-inflammatory effects. The aim is to provide new insights into the prevention and treatment of inflammatory diseases.


Subject(s)
Cannabinoid Receptor Modulators/pharmacology , Cannabinoid Receptor Agonists/pharmacology , Receptors, Cannabinoid , Cannabinoids/pharmacology , Anti-Inflammatory Agents/pharmacology
2.
China Journal of Chinese Materia Medica ; (24): 4302-4319, 2023.
Article in Chinese | WPRIM | ID: wpr-1008685

ABSTRACT

Traditional Chinese medicine Scrophulariae Radix, which is also called Yuan Shen, black Shen, is the dried root of Scrophularia ningpoensis of the Scrophulariaceae family. Research has indicated that the chemical constituents of Scrophulariae Radix mainly include terpenoids, phenylpropanoids, organic acids, volatile oils, steroids, sugars, flavonoids, alkaloids and phenols, among which iridoids and phenylpropanoids were the main active constituents. It has been reported that extracts of Scrophulariae Radix or its active substances have anti-inflammatory, antioxidant, hepatoprotective, anti-tumor, anti-fatigue, uric acid-lowering, anti-depression, myocardial cell-protective and other pharmacological activities, and can regulate cardiovascular system, central nervous system and immune system. This paper reviewed the present research achievements of Scrophulariae Radix in chemical constituents, pharmacological activities, processing methods, toxicity and other aspects, and the clinical application of Scrophulariae Radix in ancient and modern times was illustrated. This paper aimed to provide reference for further research of Scrophulariae Radix and facilitated its clinical application.


Subject(s)
Medicine, Chinese Traditional , Drugs, Chinese Herbal/chemistry , Chromatography, High Pressure Liquid , Plant Roots/chemistry , Scrophularia/chemistry
3.
Chinese Pharmacological Bulletin ; (12): 1346-1353, 2023.
Article in Chinese | WPRIM | ID: wpr-1013756

ABSTRACT

Aim To investigate the protective effect of orcinol glucoside on dexamethasone(DEX)-induced osteoblast injury and its mechanism. Methods Primary osteoblasts were extracted from calvaria of neonatal mice and cultured in medium with DEX(1 μmol•L

4.
China Journal of Chinese Materia Medica ; (24): 1727-1737, 2021.
Article in Chinese | WPRIM | ID: wpr-879086

ABSTRACT

Methotrexate(MTX) is a commonly used antimetabolite, which can be used in the treatment of a variety of diseases. However, hepatotoxicity in the use of MTX severely limits its clinical use. Therefore, how to prevent and treat hepatotoxicity of MTX has become an urgent clinical problem. This paper summarizes and analyzes relevant literatures on the prevention and treatment of hepa-totoxicity caused by MTX with traditional Chinese medicines and natural medicines in recent years. MTX-induced hepatotoxicity mechanisms include folate pathway, oxidative stress damage and adenosine pathway, of which oxidative stress theory is the main research direction. A total of 14 kinds of traditional Chinese medicine and natural medicine extracts including white peony root, and 21 kinds of natural monomer compounds, including berberine, play an anti-MTX-induced hepatotoxic effect by resisting oxidative stress, inhibiting inflammation and regulating signal pathways. According to current studies on the prevention and treatment of hepatotoxicity induced by MTX with traditional Chinese medicines and natural medicines, there are insufficiencies, such as partial and superficial mechanism studies, inadequate combination of experimental research and clinical practice, non-standard experimental design and lack of application of advanced technologies and methods. This paper systematically reviewed the effects and mechanisms of traditional Chinese medicines and natural medicines against hepatotoxicity induced by MTX and defined current studies and deficiencies, in the expectation of proposing new study strategies and directions and providing scientific basis for rational clinical use of MTX and development of new drugs against MTX hepatotoxicity.


Subject(s)
Humans , Chemical and Drug Induced Liver Injury/prevention & control , Drug-Related Side Effects and Adverse Reactions , Liver/metabolism , Medicine, Chinese Traditional , Methotrexate/toxicity , Oxidative Stress
5.
China Journal of Chinese Materia Medica ; (24): 3824-3831, 2021.
Article in Chinese | WPRIM | ID: wpr-888104

ABSTRACT

The present study aimed to provide the protection strategies for wild germplasm resources of original plants of Viticis Fructus and a theoretical basis for the sustainable use of Viticis Fructus. The genetic diversity and genetic structures of the 232 indivi-duals in 19 populations of Vitex rotundifolia and V. trifolia were analyzed by eight SSR markers with tools such as Popgene32, GenAlex 6.502, and STRUCTURE. Bottleneck effect was detected for the population with more than 10 individuals. The results indicated that 42 and 26 alleles were detected from the populations of V. rotundifolia and V. trifolia, respectively, with average expected heterozygo-sities of 0.448 6 and 0.583 9, which are indicative of low genetic diversity. AMOVA revealed the obvious genetic variation of V. rotundifolia and V. trifolia within population(84.43%, P<0.01; 60.37%, P<0.01). Furthermore, in eight SSR loci, six from V. rotundifolia populations and two from V. trifolia populations failed to meet Hardy-Weinberg equilibrium expectations(P<0.05), which confirmed that the populations experienced bottleneck effect. As assessed by Mantel test, geographical distance posed slight impacts on the genetic variation between the populations of V. rotundifolia and V. trifolia. Principal component analysis(PCA) and STRUCTURE analysis demonstrated evident introgression of genes among various populations. The original plants of Viticis Fructus were confirmed low in genetic diversity and genetic differentiation level. Therefore, the protection of wild resources of original plants of Viticis Fructus should be strengthened to ensure its sustainable use.


Subject(s)
Alleles , Fruit/genetics , Genetic Variation , Geography , Microsatellite Repeats , Vitex/genetics
6.
China Journal of Chinese Materia Medica ; (24): 3540-3550, 2021.
Article in Chinese | WPRIM | ID: wpr-888005

ABSTRACT

Cannabinoid receptor type 2( CB2 R),a member of the G protein-coupled receptor( GPCR) superfamily,has a variety of biological activities,such as regulating pain response,resisting inflammation and fibrosis,and mediating bone metabolism. Some CB2 R regulators exhibit a good regulatory effect on bone metabolism. Cannabinoids in Cannabis sativa can cause psychoactive effects despite various pharmacological actions they exerted by targeting CB2 R. Therefore,it is of great significance to discover CB2 R regulators in non-Cannabis plants for finding new lead compounds without psychoactive effects and elucidating the action mechanism of plant drugs. The present study clarifies the discovery,structure,and physiological functions of CB2 R,especially its regulatory effects on bone metabolism,summarized CB2 R regulators extracted from non-Cannabis plants,and systematically analyzes the regulatory effects of CB2 R regulators on bone metabolism in animals,osteoblasts,and osteoclasts,to provide a scientific basis for the discovery of new CB2 R regulators and the development of anti-osteoporotic drugs.


Subject(s)
Animals , Cannabinoids/pharmacology , Cannabis , Osteoblasts , Osteoclasts , Receptors, Cannabinoid
7.
Chinese journal of integrative medicine ; (12): 31-38, 2021.
Article in English | WPRIM | ID: wpr-880494

ABSTRACT

OBJECTIVE@#To systematically evaluate the protective effects of Humulus lupulus L. extract (HLE) on osteoporosis mice.@*METHODS@#In vivo experiment, a total of 35 12-week-old female ICR mice were equally divided into 5 groups: the sham control group (sham); the ovariectomy with vehicle group (OVX); the OVX with estradiol valerate [EV, 0.2 mg/(kg•d)] the OVX with low- or high-dose HLE groups [HLE, 1 g/(kg•d) and 3 g/(kg•d)], 7 in each group. Treatment began 1 week after the ovariectomized surgery and lasted for 12 weeks. Bone mass and trabecular bone mircoarchitecture were evaluated by micro computed tomography, and bone turnover markers in serum were evaluated using enzyme-linked immunosorbent assay (ELISA) kits. In vitro experiment, osteoblasts and osteoclasts were treated with HLE at doses of 0, 4, 20 and 100 µg/mL. Biomarkers for bone formation in osteoblasts and bone resorption in osteoclasts were analyzed.@*RESULTS@#Compared with the OVX group, HLE exerted bone protective effects by the increase of estradiol (P<0.05), the improvement of cancellous bone structure, bone mineral density (P<0.01) and the reduction of serum alkaline phosphatase (ALP), tartrate resistant acid phosphatase (TRAP), bone gla-protein, c-terminal telopeptides of type I collagen (CTX-I) and deoxypyridinoline levels (P<0.01 for all). In vitro experiment, compared with the control group, HLE at 20 µg/mL promoted the cell proliferation (P<0.01), and increased the expression of bone morphogenetic protein-2 and osteopontin levels in osteoblasts (both P<0.05). HLE at 100 µg/mL increased the osteoblastic ALP activities, and HLE at all dose enhanced the extracellular matrix mineralization (both P<0.01). Furthermore, compared with the control group, HLE at 20 µg/mL and 100 µg/mL inhibited osteoclastic TRAP activity (P<0.01), and reduced the expression of matrix metalloproteinase-9 and cathepsin K (both P<0.05).@*CONCLUSION@#HLE may protect against bone loss, and have potentials in the treatment of osteoporosis.

8.
Chinese Journal of Natural Medicines (English Ed.) ; (6): 401-416, 2020.
Article in English | WPRIM | ID: wpr-827229

ABSTRACT

Rubus chingii Hu, a member of the rosaceae family, is extensively distributed in China and Japan. Its unripe fruits (Fupenzi in Chinese) have a long history of use as an herbal tonic in traditional Chinese medicine for treating various diseases commonly associated with kidney deficiency, and they are still in use today. Phytochemical investigations on the fruits and leaves of R. chingii indicate the presence of terpenoids, flavonoids, steroids, alkaloids, phenylpropanoids, phenolics, and organic acids. Extracts or active substances from this plant are reported to have various pharmacological properties, including antioxidant, anti-inflammatory, antitumor, antifungal, antithrombotic, antiosteoporotic, hypoglycemic, and central nervous system-regulating effects. This review provides up-to-date information on the botanical characterizations, traditional usages, chemical constituents, pharmacological activities, toxicity, and quality control of R. chingii. Possible directions for future research are also briefly proposed. This review aims to supply fundamental data for the further study of R. chingii and contribute to the development of its clinical use.

9.
Academic Journal of Second Military Medical University ; (12): 1130-1134, 2019.
Article in Chinese | WPRIM | ID: wpr-838062

ABSTRACT

Post-stroke cognitive impairment (PSCI) is an important cause of post-stroke disability, and it is also one of focuses of stroke research. The incidence of PSCI is high, which affects the recovery of neurologic function and lowers the quality of life of patients. Therefore, neurologists should be alert to PSCI, and guide patients to actively prevent PSCI to improve the prognosis. In this paper, we reviews the research status of the incidence, influencing factors, neuropsychological assessment, imaging research and prevention measures of PSCI.

10.
China Journal of Chinese Materia Medica ; (24): 2046-2050, 2019.
Article in Chinese | WPRIM | ID: wpr-773130

ABSTRACT

The endophytic fungi from root,main stem,branch and leaf of Scrophularia ningpoensis were isolated from Zhejiang,whether these strains could yield harpagide or harpagoside were tested by HPLC and LC-MS. According to the morphological characteristic and the similarity of the nucleotide sequence of internal transcribed spacer( ITS) between r DNAs,the strains producing harpagide or harpagoside were identified. The results showed that 210 strains were isolated from the samples,which were classified into 9 orders,13 families and 17 genera by morphological study. Harpagide was detected in endogenous fungi ZJ17 and harpagoside was detected in endogenous fungi ZJ25 by HPLC coupled with LC-MS. ZJ17 was identified as Alternaria alternate and ZJ25 was identified as A.gaisen by its morphology and authenticated by ITS( ITS4 and ITS5 regions and the intervening 5. 8 S rDNA region).


Subject(s)
China , DNA, Fungal , Genetics , DNA, Ribosomal Spacer , Genetics , Endophytes , Classification , Metabolism , Fungi , Classification , Metabolism , Glycosides , Iridoid Glycosides , Metabolism , Pyrans , Metabolism , Scrophularia , Microbiology
11.
China Journal of Chinese Materia Medica ; (24): 1825-1829, 2017.
Article in Chinese | WPRIM | ID: wpr-256087

ABSTRACT

Hops, the female inflorescences of the hop plant (Humulus lupulus), are widely used in the brewing industry to add bitterness and aroma to beer. Combining with the relevant literature, the chemical composition(resinae, volatile oil, polyphenol and polysaccharide) in hops and their pharmacological effects are reviewed in this paper so as to present some sights for further application research and development.

12.
Acta Pharmaceutica Sinica ; (12): 936-942, 2017.
Article in Chinese | WPRIM | ID: wpr-779677

ABSTRACT

Cathepsin K (CTSK) is considered a critical pharmaceutical target in the treatment of osteoporosis. CTSK exerts proteolytic activities against regulatory proteins besides its collagenase function, which may account for some of the adverse reactions when blocked by active site-directed inhibitors. Exosite inhibitors that can discriminate between the therapeutic collagenase and other biological activities of CTSK specifically inhibit the collagenase activity of CTSK without interfering with the other proteolytic activities of the protease. Active recombinant CTSK was expressed in Pichia pastoris, and purified by n-butyl sepharose and SP sepharose column chromatography. Herba Ecliptae is a common traditional Chinese medicine in the treatment of bone diseases. Collagenase assay and benzyloxycarbonyl-Phe-Arg-7-amido-4-methylcoumarin (Z-FR-MCA) substrate assay based on CTSK are applied to verify the exosite inhibitors. n-Butanol extract of Herba Ecliptae are the most active fraction and eclalbasaponin IX isolated from n-butanol fraction is the potential exosite inhibitor of CTSK.

13.
China Journal of Chinese Materia Medica ; (24): 1602-1607, 2016.
Article in Chinese | WPRIM | ID: wpr-279200

ABSTRACT

The paper aims to study the effects of endophytic fungi from D. officinale cultivated on living trees on growth and components metabolism of tissue culture seedlings. Morphological characteristics and agronomic characters of tissue culture seedlings infected and uninfected by endophytic fungus were observed and measured. Polysaccharides and alcohol-soluble extracts contents were determined by phenol-sulfuric acid method and hot-dipmethod, respectively. Monosacchride composition of polysaccharides and alcohol-soluble extracts components were analyzed by pre-column derivatives HPLC and HPLC method, respectively. It showed that effects of turning to purple of stem nodes could be changed by endophytic fungus. Besides, the endophytic fungus could affect the contents and constitutions of polysaccharides and alcohol-soluble extracts. The strains tested, expect DO34, could promote growth and polysaccharides content of tissue culture seedlings. The strains tested, expect DO12, could promote the accumulation of mannose. Furthermore, DO18, DO19 and DO120 could increase alcohol-soluble extracts. On the basis, four superior strains were selected for mechanism research between endophytic fungus and their hosts and microbiology engineering.

14.
Chinese Journal of Natural Medicines (English Ed.) ; (6): 413-420, 2016.
Article in English | WPRIM | ID: wpr-812616

ABSTRACT

There is an increasing interest in phytoestrogens due to their potential medical usage in hormone replacement therapy (HRT). The present study was designed to investigate the in vitro effects of estrogen-like activities of two widespread coumarins, osthole and imperatorin, using the MCF-7 cell proliferation assay and their alkaline phosphatase (ALP) activities in osteoblasts Saos-2 cells. The two compounds were found to strongly stimulate the proliferation of MCF-7 cells. The estrogen receptor-regulated ERα, progesterone receptor (PR) and PS2 mRNA levels were increased by treatment with osthole and imperatorin. All these effects were significantly inhibited by the specific estrogen receptor antagonist ICI182, 780. Cell cycle analysis revealed that their proliferation stimulatory effect was associated with a marked increase in the number of MCF-7 cells in S phase, which was similar to that observed with estradiol. It was also observed that they significantly increased ALP activity, which was reversed by ICI182,780. These results suggested that osthole and imperatorin could stimulate osteoblastic activity by displaying estrogenic properties or through the ER pathway. In conclusion, osthole and imperatorin may represent new pharmacological tools for the treatment of osteoporosis.


Subject(s)
Humans , Alkaline Phosphatase , Genetics , Metabolism , Cell Line, Tumor , Cell Proliferation , Cnidium , Chemistry , Coumarins , Pharmacology , Drugs, Chinese Herbal , Pharmacology , Furocoumarins , Pharmacology , MCF-7 Cells , Osteoblasts , Cell Biology , Phytoestrogens , Pharmacology , Receptors, Estrogen , Genetics , Metabolism
15.
Chinese Journal of Natural Medicines (English Ed.) ; (6): 163-182, 2015.
Article in English | WPRIM | ID: wpr-812159

ABSTRACT

Salvia miltiorrhiza Bunge (SM) is a very popular medicinal plant that has been extensively applied for many years to treat various diseases, especially coronary heart diseases and cerebrovascular diseases, either alone or in combination with other Chinese plant-based medicines. Although a large number of studies on SM have been performed, they are scattered across a variety of publications. The present review is an up-to-date summary of the published scientific information about the traditional uses, chemical constituents, pharmacological effects, side effects, and drug interactions with SM, in order to lay the foundation for further investigations and better utilization of SM. SM contains diverse chemical components including diterpenoid quinones, hydrophilic phenolic acids, and essential oils. Many pharmacological studies have been done on SM during the last 30 years, focusing on the cardiovascular and cerebrovascular effects, and the antioxidative, neuroprotective, antifibrotic, anti-inflammatory, and antineoplastic activities. The research results strongly support the notion that SM has beneficial therapeutic properties and has a potential of being an effective adaptogenic remedy.


Subject(s)
Humans , Drugs, Chinese Herbal , Pharmacology , Therapeutic Uses , Medicine, Chinese Traditional , Salvia miltiorrhiza , Chemistry
16.
China Journal of Chinese Materia Medica ; (24): 325-330, 2013.
Article in Chinese | WPRIM | ID: wpr-346824

ABSTRACT

<p><b>OBJECTIVE</b>The research aimed to investigate the entophytic fungal community of Cynanchum Komarrovii, including the biodiversity in different organs and the correlations with ecological environment. Endophytic fungi with patent bioactivity were also rapidly screened.</p><p><b>METHOD</b>PDA medium was used to isolate and purify the endophytic fungi from C. komarovii living in Shaanxi and Ningxia district, respectively. The strains were identified based on the morphological characteristics of the fungi and similarity of 5.8S gene and internal transcribed spacer (ITS) sequence. Pyriculaia oryzae model was applied to preliminarily screen the active fungi.</p><p><b>RESULT</b>Ninety-four strains of endophytic fungi were isolated and identified to 9 species, 13 genera, 9 families and 6 orders, among them, 47 strains were from the plants living in Ningxia. And then, 5 of them were isolated from roots, 14 from branches, and 28 from leaves. They were identified belonging to 8 species, 9 genera, 5 families and 4 orders. Additionally, 47 strains were from the plants living in Shaanxi. 16 were isolated from the roots, 18 from branches, 13 from leaves. They were identified belonging to 5 species, 8 genera, 6 families and 4 orders. By preliminary screening, 18 strains of endophytes completely inhibited the germination of conidium, which showed a potential bioactivity for these fungi. Both N4 and S17 strains had stronger growth inhibition effect.</p><p><b>CONCLUSION</b>Endophytic fungi from desert plant C. komarovii have the feature of diversity. Different geographical environment and type of organizations lead to the significant difference on the quantity and the species composition. Most of fungi in Ningxia C. komarovii distribute in leaves. However, most of those in Shaanxi C. komarovii distribute in stems and leaves. It also indicated that endophytes from C. komarovii had a strong antifungal activity.</p>


Subject(s)
Antifungal Agents , Pharmacology , Biodiversity , China , Culture Media, Conditioned , Pharmacology , Cynanchum , Microbiology , DNA, Ribosomal Spacer , Genetics , Desert Climate , Endophytes , Classification , Genetics , Fungi , Classification , Genetics , Genetic Variation , Magnaporthe , Microbial Sensitivity Tests , Phylogeny , Plant Leaves , Microbiology , Plant Roots , Microbiology , Plant Stems , Microbiology , Genetics , Species Specificity
17.
Chinese Journal of Natural Medicines (English Ed.) ; (6): 673-675, 2013.
Article in English | WPRIM | ID: wpr-812643

ABSTRACT

AIM@#To investigate the chemical constituents of the endophytic fungus Verticillium sp. isolated from Rehmannia glutinosa.@*METHODS@#The compounds were isolated and purified by repeated column chromatography, and their structures were determined on the basis of physicochemical properties and spectral analysis. Their cytotoxic and antifungal activities were evaluated.@*RESULTS@#Ten compounds were obtained and their structures were identified as 2, 4-dihydroxy-2', 6-diacetoxy-3'-methoxy-5'-methyl-diphenyl ether (1), paecilospirone (2), α-acetylorcinol (3), 2-methoxy-1,8-dimethyl-xanthen-9-one (4), 4-hydroxy-α-lapachone (5), enalin A (6), 2,3,4-trimethyl-5,7-dihydroxy-2,3-dihydrobenzofuran (7), 4-hydroxyethyl-phenol (8), 2,4-dihydroxy-3,5,6-trimethyl- methylbenzoate (9), and 3-isopropenyl-(Z)-monomethyl maleate (10).@*CONCLUSIONS@#Compound 1 is a new diphenyl ether, and showed cytotoxic activity against HL-60 cells (IC50 2.24 μg · mL(-1)), and antifungal activities against Candida albicans (MIC 8 μg · mL(-1)) and Aspergillus fumigatus (MIC 16 μg · mL(-1)).


Subject(s)
Humans , Antifungal Agents , Chemistry , Metabolism , Pharmacokinetics , Antineoplastic Agents , Chemistry , Metabolism , Pharmacokinetics , Aspergillus fumigatus , Candida albicans , Cell Line, Tumor , Endophytes , Chemistry , Metabolism , Phenyl Ethers , Chemistry , Metabolism , Pharmacokinetics , Rehmannia , Microbiology , Verticillium , Chemistry , Metabolism
18.
Article in English | IMSEAR | ID: sea-131138

ABSTRACT

The optimization conditions for extraction of the lignans from Schisandra chinensis (Turcz.) including the proportion between ethanol and water (A), reflux time (B), extraction time (C) and solvent volume (D) were investigated through an orthogonal design of L₉(3⁴). HPLC was used to determine the schisandrin, deoxyschisandrin and \γ-schisandrin in the plant. It was found that the optimized conditions of extraction were refluxing twice with 95% ethanol, volume 10 times of the dried powder weight (ml) for 90 min. Additionally, adsorption capacity on macroporous resins, ratio of sample to solvent volume and elution of various concentrations of the ethanol extract for purification of the lignans were optimized in this study. From the results, the maximum adsorption capacities of schisandrin, deoxyschisandrin and \γ-schisandrin were found to be 0.16, 0.75 and 0.62 mg/g resin, respectively. The adsorbed processing at volume 8 BV and the ratio of sample to solvent volume of 10:125 was also obtained. Seventy percent ethanol was the most suitable eluent to get the highest yield of the lignans as adsorbed by the macroporous resin.

19.
Journal of Pharmaceutical Practice ; (6): 67-70, 2001.
Article in Chinese | WPRIM | ID: wpr-790296

ABSTRACT

In this paper,the background,present situation,problem and tactics of GAP(Good Agricultural Practice)of chinese materia medica are discussed.The main problems of the yielding of chinese materia medica are as followings:(1)Lack of close controlling standards and scientific detecting methods.(2)Decentralized management.low benefit and low controllability.(3)The pesticide residue and heavy metal content exceeding the provided standard.(4)Production and marketing disjointed,supervising and controlling intensity in the whole yielding process not enough.Thus,3 measures are put forward:(1)Strengthening the management of the quality of chinese materia medica,formulating strict and unitary quality controlling standards,setting up scientific checking methods.(2)Developing genuine drugs,establishing famous brands.(3)Establishing green chinese meateria medica yielding bases,to make the Chinese Materia Medica utilization sustainable.

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