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The Tibetan people's knowledge on preserving health is an important part of Tibetan medical culture. Most of the Tibetans live on the plateau where it is cold with decreased oxygen. They are devout Buddhists and they have developed a variety of healthy folk customs. These factors form the health culture of Tibetan medicine and demonstrate the plateau characteristics of health, psychology health and health customs. The health culture of Tibetan medicine has far-reaching influence because of the spread of Buddhism. Therefore it is worth exploring and carrying forward.

Zuota is regarded as the king of Tibetan medicine. However, due to the confidentiality of this precious medicine, the scientific characterization of Zuota is very scarce, which limits the pharmacology and biosafety studies of Zuota. Herein, we collected four different Zuota samples from Tibet, Qinghai, Gansu, and Sichuan and characterized them by multiple techniques. Our results showed that Zuota was mainly an inorganic mixture of HgS, sulfur, and graphite. Morphologically, Zuota samples were composed of nanoparticles, which further aggregated into microsized particles. Chemically, the majorities of Zuota were S and Hg (in the forms of HgS and pure sulfur). All samples contained pure sulfur with orthorhombic crystalline. Zuota from Qinghai province had different HgS crystalline, namely, hexagonal crystalline. The others were all face-centered cubic crystalline. Carbon in Zuota NPs was in the form of graphite. The implication to future studies of Zuota was discussed.

Zuota is regarded as the king of Tibetan medicine. However, due to the confidentiality of this precious medicine, the scientific characterization of Zuota is very scarce, which limits the pharmacology and biosafety studies of Zuota. Herein, we collected four different Zuota samples from Tibet, Qinghai, Gansu, and Sichuan and characterized them by multiple techniques. Our results showed that Zuota was mainly an inorganic mixture of HgS, sulfur, and graphite. Morphologically, Zuota samples were composed of nanoparticles, which further aggregated into microsized particles. Chemically, the majorities of Zuota were S and Hg (in the forms of HgS and pure sulfur). All samples contained pure sulfur with orthorhombic crystalline. Zuota from Qinghai province had different HgS crystalline, namely, hexagonal crystalline. The others were all face-centered cubic crystalline. Carbon in Zuota NPs was in the form of graphite. The implication to future studies of Zuota was discussed.

Zuota is regarded as the king of Tibetan medicine. However, due to the confidentiality of this precious medicine, the scientific characterization of Zuota is very scarce, which limits the pharmacology and biosafety studies of Zuota. Herein, we collected four different Zuota samples from Tibet, Qinghai, Gansu, and Sichuan and characterized them by multiple techniques. Our results showed that Zuota was mainly an inorganic mixture of HgS, sulfur, and graphite. Morphologically, Zuota samples were composed of nanoparticles, which further aggregated into microsized particles. Chemically, the majorities of Zuota were S and Hg (in the forms of HgS and pure sulfur). All samples contained pure sulfur with orthorhombic crystalline. Zuota from Qinghai province had different HgS crystalline, namely, hexagonal crystalline. The others were all face-centered cubic crystalline. Carbon in Zuota NPs was in the form of graphite. The implication to future studies of Zuota was discussed.

The essential oil of Tibetan medicine Dracocephalum heterophyllum Benth was obtained by hydrodistillation with a 0.7% (v/w) yield. The chemical composition of the essential oil was analyzed by gas chromatography-mass spectral (GC-MS). Eighty-three compounds, constituting about 89.83% of the total oil, were identified. The main compound in the oil were Cineole (14.89%), trans-nerolido (7.10%), 1-m-ethyl-2-(1-methylethyl)-benzene (4.42%), Germacrene-D (4.84%), Decahydro-1,1,4,7-tetramethyl-4aH-cycloprop[e]azulen-4a-ol (4.94%), p-menth-1-en-4-ol,acetate (4.34%), 4-methyl-1-(1-methylethyl)-3-cyclohexen-1-ol (4.10%). The antimicrobial activity of the oil was evaluated against nine bacterial, one yeast, and three fungi. The antimicrobial test result showed that the essential oil strongly inhibited the growth of test microorganisms studied. The maximal inhibition zones and MIC values for bacterial, yeast and fungi strain were in the range of 18-25 mm and 0.039-0.156 mg mL(-1); *20 mm, and 0.156 mg mL(-1); 8-24 mm and 0.313-2.5 mg mL(-1); respectively. The antioxidant activity of the oil was determined by the malonyldialdehyde (MDA) test, measuring the MDA concentration in mouse liver cell microsomal after induced lipid peroxidation using FeSO(4) and ascorbic acid, The inhibition of lipid peroxidation was 59.3% with a concentration of 0.5 mg mL(-1). Result presented here may suggest that the essential oil of D. heterophyllum posses antimicrobial and antioxidant properties, and therefore, they can be one of new medicinal resources for antimicrobial agent and/or used as a natural preservative ingredient in food and cosmetics and pharmaceuticals industry.

The essential oil of Tibetan medicine Dracocephalum heterophyllum Benth was obtained by hydrodistillation with a 0.7% (v/w) yield. The chemical composition of the essential oil was analyzed by gas chromatography-mass spectral (GC-MS). Eighty-three compounds, constituting about 89.83% of the total oil, were identified. The main compound in the oil were Cineole (14.89%), trans-nerolido (7.10%), 1-m-ethyl-2-(1-methylethyl)-benzene (4.42%), Germacrene-D (4.84%), Decahydro-1,1,4,7-tetramethyl-4aH-cycloprop[e]azulen-4a-ol (4.94%), p-menth-1-en-4-ol,acetate (4.34%), 4-methyl-1-(1-methylethyl)-3-cyclohexen-1-ol (4.10%). The antimicrobial activity of the oil was evaluated against nine bacterial, one yeast, and three fungi. The antimicrobial test result showed that the essential oil strongly inhibited the growth of test microorganisms studied. The maximal inhibition zones and MIC values for bacterial, yeast and fungi strain were in the range of 18-25 mm and 0.039-0.156 mg mL(-1); *20 mm, and 0.156 mg mL(-1); 8-24 mm and 0.313-2.5 mg mL(-1); respectively. The antioxidant activity of the oil was determined by the malonyldialdehyde (MDA) test, measuring the MDA concentration in mouse liver cell microsomal after induced lipid peroxidation using FeSO(4) and ascorbic acid, The inhibition of lipid peroxidation was 59.3% with a concentration of 0.5 mg mL(-1). Result presented here may suggest that the essential oil of D. heterophyllum posses antimicrobial and antioxidant properties, and therefore, they can be one of new medicinal resources for antimicrobial agent and/or used as a natural preservative ingredient in food and cosmetics and pharmaceuticals industry.

Minerals are alchemically processed as Bhasmas in Ayurvedic medicines or as Zuotai in Tibetan medicines. Ayurveda is a knowledge system of longevity and considers the mineral elixir made from "nature" capable of giving humans perpetual life. Herbo-metallic preparations have a long history in the treatment of various diseases in India, China, and around the world. Their disposition, pharmacology, efficacy, and safety require scientific evaluation. This review discusses the Bhasmas in Ayurvedic medicines and Zuotai in Tibetan medicines for their occurrence, bioaccessibility, therapeutic use, pharmacology, toxicity, and research perspectives. A literature search on Mineral, Bhasma, Ayurvedic medicine, Zuotai, Tibetan medicine, and Metals/metalloids from PubMed, Google and other sources was carried out, and the relevant papers on their traditional use, pharmacology, and toxicity were selected and analyzed. Minerals are processed to form Bhasma or Zuotai to alter their physiochemical properties distinguishing them from environmental metals. The metals found in Ayurveda are mainly from the intentional addition in the form of Bhasma or Zuotai. Bhasma and Zuotai are often used in combination with other herbals and/or animal-based products as mixtures. The advanced technologies are now utilized to characterize herbo-metallic preparations as Quality Assurance/Quality Control. The bioaccessibility, absorption, distribution, metabolism, and elimination of herbo-metallic preparations are different from environmental metals. The pharmacological basis of Bhasma in Ayurveda and Zuotai in Tibetan medicines and their interactions with drugs require scientific research. Although the toxic potentials of Bhasma and Zuotai differ from environmental metals, the metal poisoning case reports, especially lead (Pb), mercury (Hg), and arsenic (As) from inappropriate use of traditional medicines, are increasing, and pharmacovigilance is desired. In risk assessment, chemical forms of metals in Bhasma and Zuotai should be considered for their disposition, efficacy, and toxicity.

Minerals are alchemically processed as Bhasmas in Ayurvedic medicines or as Zuotai in Tibetan medicines. Ayurveda is a knowledge system of longevity and considers the mineral elixir made from "nature" capable of giving humans perpetual life. Herbo-metallic preparations have a long history in the treatment of various diseases in India, China, and around the world. Their disposition, pharmacology, efficacy, and safety require scientific evaluation. This review discusses the Bhasmas in Ayurvedic medicines and Zuotai in Tibetan medicines for their occurrence, bioaccessibility, therapeutic use, pharmacology, toxicity, and research perspectives. A literature search on Mineral, Bhasma, Ayurvedic medicine, Zuotai, Tibetan medicine, and Metals/metalloids from PubMed, Google and other sources was carried out, and the relevant papers on their traditional use, pharmacology, and toxicity were selected and analyzed. Minerals are processed to form Bhasma or Zuotai to alter their physiochemical properties distinguishing them from environmental metals. The metals found in Ayurveda are mainly from the intentional addition in the form of Bhasma or Zuotai. Bhasma and Zuotai are often used in combination with other herbals and/or animal-based products as mixtures. The advanced technologies are now utilized to characterize herbo-metallic preparations as Quality Assurance/Quality Control. The bioaccessibility, absorption, distribution, metabolism, and elimination of herbo-metallic preparations are different from environmental metals. The pharmacological basis of Bhasma in Ayurveda and Zuotai in Tibetan medicines and their interactions with drugs require scientific research. Although the toxic potentials of Bhasma and Zuotai differ from environmental metals, the metal poisoning case reports, especially lead (Pb), mercury (Hg), and arsenic (As) from inappropriate use of traditional medicines, are increasing, and pharmacovigilance is desired. In risk assessment, chemical forms of metals in Bhasma and Zuotai should be considered for their disposition, efficacy, and toxicity.

Objective: To investigate the chemical constituent from the roots of Gentiana straminea.; Methods: The constituents were separated by microporous resin,silica gel,Sephadex LH-20 and preparative column chromatography and their structures were elucidated by NMR and MS spectral methods.; Results: Twelve chemical constituents were isolated from the roots of Gentiana straminea and their structures were identified as daucosterol( 1),β-sitosterol( 2),ursolic acid( 3),sweroside( 4),swertiamarin( 5),gentiopicroside( 6),6’-O-acetyl-gentiopicroside( 7),6’-O-β-D-glucopyranosyl-sweroside( 8),protocatech uic aldehyde( 9),protocatechuic acid( 10),methyl gallate( 11) and dibutyl phthalate( 12).; Conclusion: The compounds 8,9,10,11 and 12 are obtained from this plant for the first time.;

Meconopsis horridula Hook.f. Thoms has been used as a traditional Tibetan medicine to clear away heat, relieve pain, and mobilize static blood. In this study, a reliable method based on high-performance liquid chromatography with diode array detection and electrospray ionization quadrupole time-of-flight tandem mass spectrometry was established for the identification of components in this herb. A total of 40 compounds (including 17 flavonoids, 15 alkaloids, and eight phenylpropanoids) were identified or tentatively identified. Among them, 17 components were identified in the herb for the first time. Compound 39 appears to be a novel compound, which is confirmed as 3-(kaempferol-8-yl)-2,3-epoxyflavanone by NMR spectroscopy and mass spectrometry. Moreover, seven major constituents were simultaneously quantified by the developed high-performance liquid chromatography with tandem triple-quadrupole mass spectrometry method. The quantitative method was validated and quality parameters were established. The study provides a comprehensive approach for understanding this herbal medicine.

Meconopsis horridula Hook.f. Thoms has been used as a traditional Tibetan medicine to clear away heat, relieve pain, and mobilize static blood. In this study, a reliable method based on high-performance liquid chromatography with diode array detection and electrospray ionization quadrupole time-of-flight tandem mass spectrometry was established for the identification of components in this herb. A total of 40 compounds (including 17 flavonoids, 15 alkaloids, and eight phenylpropanoids) were identified or tentatively identified. Among them, 17 components were identified in the herb for the first time. Compound 39 appears to be a novel compound, which is confirmed as 3-(kaempferol-8-yl)-2,3-epoxyflavanone by NMR spectroscopy and mass spectrometry. Moreover, seven major constituents were simultaneously quantified by the developed high-performance liquid chromatography with tandem triple-quadrupole mass spectrometry method. The quantitative method was validated and quality parameters were established. The study provides a comprehensive approach for understanding this herbal medicine.

In order to illuminate the effective compounds in Tibetan medicine kandrakari, chemical composition of dry stems of Rubus amabilis were studied by means of various chromatographic techniques, leading to the isolation of 11 compounds. On the basis of spectroscopic data, their structures were elucidated as 1,8-dihydroxy-3,7-dimethoxyxanthone (1), 1-hydroxy-3,7,8-trimethoxyxanthone (2), 1,8-dihydroxy-3,5-dim ethoxyxanthone (3), kaempfero-3-O-(6"-trans-p-coumaroyl) -beta-D-glucopyranoside (4), quercetin (5), kaempferol (6), hyperoside (7), luteolin-7-O-beta-D-glucopy ranoside (8), apigenin-7-O-beta-D-glucopyranoside (9), isovitexin-7-O-glucoside (10), and procyanidin B4 (11). Compounds 1-3 were isolated from the Rubus genus for the first time,and compounds 1-6, 10-11 were isolated from R. amabilis for the first time.

OBJECTIVE: To compare the ettect and side-ettect of fluoxetine and combination of fluoxetine and Chinese or Tibetan medicine in treating senile depression in plateau district. Methods Ninety patients with diagnosis of senile depression conformed to CCMD-3 standard, in plateau district of 2260 - 3200 m altitude were randomly divided into three groups and treated with fluoxetine (group A), fluoxetine plus Sanpu Xinnao Xin granule (group B) and fluoxetine plus Xiaoyao pill (group C), respectively, 30 cases in each group. Therapeutic effects were evaluated with Hamilton' s depressive scale (HAMD) and treatment emergent symptom scale (TESS) after 6 weeks treatment.RESULTS: There was no significant difference in the therapeutic effects between the three groups. The adverse reaction in Group B and C was less than that in Group A (P<0.01). Conclusion Sanpu Xinnao Xin granule and Xiaoyao pill can raise the tolerance of patients with senile depression in plateau area against the adverse reaction of fluoxetine.

[Objectives] By clustering analysis of tissue distribution data of brucine and strychnine in gastric ulcer model rat, the impact of Zuota on tissue distribution of basic components was studied. [Methods] Based on system clustering method of SPSS19.0 statistical analysis software, using inter-group join method and squared Euclidean distance, brucine and strychnine contents of different tissues and organs in non- Zuota group and Zuota group were taken as characteristic variables for clustering analysis, and phylogenetic tree was established. [Results] When clustering distance was 1, (i) taking brucine content as the index, there were three kinds of convergences in non-Zuota group. A1 class: skin, liver, epididymitis and jejunum; A2 class: brain and uterus; A class: testis and muscle. Brucine contents of the three classes showed a A1 < A2 < A. There were two classes of convergences in Zuota group. B1 class : jejunum, epididymis, kidney, brain, skin and uterus; B2 class: muscle and (bottom) submandibular gland. Brucine contents of the two classes showed as B1 < B2. (ii) Taing strychnine content as the index, there were three classes of convergences in non-Zuota group. C1 class: muscle, testicle and oarrum; C2 class: heart and lung; C3 class: uterus and liver. Strychnine contents of the three classes showed a C3 <C1 < C2. There were two kinds of convergences in Zuota group. D1 class : kidney and heart; D2 class : brain tissue and uterus. Strychnine contents of the two classes showed as D1 > D2. [Conclusions] When clustering distance was 1, low-content tissues and orgas firstly clustered, and its toxicological eefect(or pharmacodynamic action)was insignificant, and this kind of tissues and organs were relatively safe. A1 class and A2 class in Zuota group were merged into B1 class, in which liver was replaced by kidney. It iilustrated that Zuota could decline the toxicity of kidney, and enlarged the safe action range of brucine. Kidney and heart in C2 class were clustered into D1 class, and average strychnine content in C2 class was higher than that of D1 class. It could be deduced that Zuota had the effect of protecting heat.

The flower buds of five <i>Lonicera</i> species, <i>Lonicera japonica</i> Thunb., <i>L. macranthoides</i> Hand.-Mazz., <i>L. hypoglauca</i> Miq., <i>L. confusa</i> DC. and <i>L. fulvotomentosa</i> Hsu et S.C. Cheng are confusable and usually utilized under the same name “Jinyinhua” in different areas for morphological similarity. Studies found that these five species possess extreme differences in chemical compounds, correspondingly showing different pharmacological activities and clinical applications. To ensure efficacy and safety of these herbal medicines and prevent unknown adverse effect, in this work, a simple, rapid and effective method combining normal light and fluorescence microscopy was developed for authentication. Surface slides and transverse sections of these buds were investigated to reveal their differences. As a routine technique, normal light microscopy which gives detailed microscopic features such as glandular hairs and nonglandular hairs, can easily distinguish four species except <i>L. confusa</i>. Fluorescence technique, which could present different distribution of fluorescence materials, is further employed to identify three species including <i>L. confusa</i> successfully. It is the first report to identify these five <i>Lonicera</i> species by combining normal light and fluorescence microscopy. This work indicated combining normal light and fluorescence microscopy could be a powerful method in authentication of confused species. Microsc. Res. Tech.74:133-141, 2011. © 2010 Wiley-Liss, Inc.

[Objectives] To explore the mechanism for the attenuate-synergistic effect of Zuota to Renqing Mangue, a contrasted study on the tissue distribution of Tibetan medicines Renqing Mangue compatible with Zuota was carried out. [Methods] The SD rats gastric ulcer model were made successfully, and then respectively were given Renqing Mangue compatible with Zuota or not according to the dose of 0.144 g/kg and normal saline by gavage administration, once a day. After 14 d of administration, various organs and tissue were isolated, including brain, heat, liver, spleen, lung, kidney, jejunum, skeletal muscle, fat, skin, submandibular gland, uterus and ovary (or testicle and epididymis). The LC-MS/MS methods were used for determining the contents of brucine and strychnine in various organs and tissue, and significant difference analysis, main target site analysis and clustering analysis were implemented. [Results] Between the Zuota group and non-Zuota group, there was extremely significat diference in the content of brucine in the liver, kidney, muscle, lung, ovary, and heart (P < 0.01), significant difference in the jeeunum (P <0.05), and no significant diference in the epididymis, testis, brain, skin and uterus (P > 0.05); the content of brucine in the submadibular gland, spleen, liver and ovary increased significantly, but significanty reduced in the kidney, muscle, jeeunum, lung and heart. And there was extremely significant diference in the content of strychnine in the liver, kidney, ovary, brain and heat (P <0.01), and no significat difference in the uterus (P > 0.05); the strychnine content increased significantly in the liver, spleen and ovary, and significanty decreased in the kidney, muscle, testis, lung, brain and heart. [Conclusions] Compatibility of Zuota can afect the distribution of brucine and strychnine in some tissue and organs, so a to achieve attenuate-synergistic effect of Zuota to Renqing Mague. [ABSTRACT FROM AUTHOR]

AIM: To identify the medicine and search for new medicine resource at the molecular level, the ITS of "Zang Yin Chen"--Swertia mussotti and its adulterant species were sequenced.METHODS: The double-stranded DNA was amplified using PCR systems 9,600 kits and sequenced on an ABI 377 automated sequencer from both directions. RESULTS: The ITS sequences of S. mussotti in different populations showed no variation. It has the unique ITS sequence and shows distinct difference from its adulterant species. In the phylogenetic tree based on the ITS data of S. mussotti and all vicarious species constructed by Paup, S. franchetiana and S. mussotti clustered together with high bootstrap support. CONCLUSION: ITS sequences can be used for the molecular authentication between the S. mussotti and its adulterant species. S. franchetiana can be regarded as a new medicine resource of "Zhang Yin Chen".

Compound Phyllanthus urinaria L (CP) is a traditional formula widely used in clinical practice for hepatocellular carcinoma (HCC), especially HBV-related HCC. HBx, HBV X gene encoded X protein, has positive correlation with the abnormal SHH pathway in HBV-related HCC. So, we predicted that CP has the capability of anti-HBV-related HCC maybe via inactivating the HBx-Hedgehog pathway axis. HepG2-HBx cells, HBx overexpression, were treated with CP (70μg/ml and 35 μg/ml, respectively) for 48 hours and the mice which received the HepG2-HBx cells were treated with CP (625mg/kg and 300 mg/kg, respectively) for 17 days to evaluate the effect of CP on HBV-related HCC. HBx could accelerate HepG2 cells proliferation, clone formation, and migration in vitro and also could strengthen tumor growth in mice. However, CP could significantly decrease HepG2-HBx cells proliferation, clone formation, and migration in vitro and also could inhibit tumors growth in mice in a dose-dependent manner. Mechanism studies suggested that HBx upregulated the mRNA and proteins expression of Sonic hedgehog (SHH), transmembrane receptor patched (PTCH-1), smoothened (SMO), oncogene homolog transcription factors-1 (GLI-1), and oncogene homolog transcription factors-2 (GLI-2), which are compositions of the SHH pathway. CP could inhibit the mRNA and proteins expression of SHH, PTCH-1, GLI-1, and HBx. It may be one of the underlying mechanisms of CP to delay the HBV-related HCC development through the HBx-SHH pathway axis inactivation. [ABSTRACT FROM AUTHOR]

The Tibetan folk medicine Qinjiao is traditionally used to treat various conditions, and its main active constituents comprise four iridoid glycosides, i.e., loganic acid, swertiamarin, gentiopicroside, and sweroside. The traditional crude medicine Qinjiao is derived from the dried roots of three species belonging to Gentiana sect. Cruciata (Gentianaceae) growing in the Qinghai-Tibetan Plateau (QTP). In this study, we determined by HPLC the contents of the four main active constituents in the dried roots collected from 83 localities at different altitudes across the QTP. The material was classified under the seven taxonomic species G. straminea, G. dahurica, G. crassicaulis, G. waltonii, G. officinalis, G. ihassica, and G. macrophylla. Our results suggested that the four constituents were present in the roots of all seven species for all localities, but their concentrations varied greatly within and between species. The level of gentiopicroside revealed to be the most dominant for all examined localities (2.1-12.4 mg/g), and G. macrophylla Pall. contained the highest concentration of all the four constituents at the species level. Except for loganic acid in G. officinalis, there was no significant correlation between the contents of these constituents and the altitude of the sampling localities. These results suggest that all species of all origins can be used as reliable resource for the crude medicine Qinjiao. However, a few species contain higher concentrations of the main active constituents, irrespective of their origin.;

To provide insights into the mechanism for the attenuate-synergistic effect of Zuota to Tibetan medicine Renqing Mangjue, a contrasted study was carried out on the pharmacokinetics of brucine and strychnine in mice plasm, which are active and toxicant ingredient in the Tibetan medicine Renqing Mangjue. LC-MS/MS was used to detect simultaneously the concentrations of brucine and strychnine in mice plasm at-different time intervals after administration parallelly and randomly, and the pharmacokinetic software Kinetica 5. 0 was selected to non-compartmental analysis (NCA) for data, and statistical analysis software SPSS 19. 0 was used for significance test on the pharmacokinetic parameters. A reliable LC-MS/MS method was established for the determination of brucine and strychnine in blood plasma, which are consistent with the requirements of the preclinical pharmacokinetic study confirmed by the methodology. The linear concentration ranges of brucine and strychnine were 0.301-104.4 µg · L(-1) (r = 0.999 5) and 0.305-106 µg · L(-1) (r = 0.999 7), respectively; The intra-day and inter-day variable coefficients were both less than 10.0% with good precision; The average extraction recoveries of brucine and strychnine were 116.23% and 112.82%, and RSD were 3.2% and 2.3% separately;The average matrix effects of brucine and strychnine were 122.48% and 116.36%, and RSD were 7.7% and 4.4%, respectively. The pharmacokinetic results showed that AUCtot of brucine and strychnine in Zuota group were both increased remarkably (P < 0.05), and the Cmax of brucine in Zuota group was about 5.25-fold higher than that of brucine in non-Zuota group (P < 0.05). The Tmax of brucine and strychnine reduced to one-eighth and one-quarter respectively compared with those in Non-Zuota group. In addition, the eliminations of brucine and strychnine in vivo were accelerated after the compatibility of Zuota. A significant difference (P < 0.05) occurred at the MRT0-t, of brucine, while the MRT0-∞ and Lz of strychnine were statistically significant upon the inspection level α = 0.1. It was found that the absorption degree of brucine and strychnine in Zuota group increased in the range of the safe dose (or concentration), while their elimination rates were accelerated, which may be one of the mechanisms for attenuate-synergistic effect of Zuota to Tibetan medicine Renqing Mangjue.

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