Rannasangpei (RSNP) is used as a therapeutic agent in the treatment of cardiovascular diseases, neurological disorders, and neurodegeneration in China; however, its potential use in the treatment of vascular dementia (VD) was unclear. In this study, our aim was to examine the neuroprotective effect of RSNP in a VD rat model, which was induced by permanent bilateral common carotid artery occlusion (2VO). Four-week administration with two doses of RSNP was investigated in our study. Severe cognitive deficit in the VD model, which was confirmed in Morris water maze (MWM) test, was significantly restored by the administration of RSNP. ELISA revealed that the treatments with both doses of RSNP could reinstate the cholinergic activity in the VD animals by elevating the production of choline acetyltransferase (ChAT) and reducing the acetylcholinesterase (AChE); the treatment of RSNP could also reboot the level of superoxide dismutase (SOD) and decrease malondialdehyde (MDA). Moreover, Western blot and quantitative PCR (Q-PCR) results indicated that the RSNP could suppress the apoptosis in the hippocampus of the VD animals by increasing the expression ratio of B-cell lymphoma-2 (Bcl-2) to Bcl-2-associated X protein (Bax). These results suggested that RSNP might be a therapeutic agent in the treatment of vascular dementia in the future.
This study sought to establish a more reliable method of identifying the "monarch" or principal drug Radix inulae and its active component alantolactone (AL) in the Tibetan medicine Manuxitang. Radix inulae and AL in Manuxitang were effectively identified by thin layer chromatography (TLC). AL was quantitatively determined using gas chromatography in the range of 0.1-1.0 mug/mL (r = 0.9998). The precision was 1.20% (n = 6) with an average RSD of 1.74%. Recovery was in the range of 93.5-98.5% with RSD value of 1.85%. The methods established were simple, accurate, and specific and could be used for quality control of Manuxitang.
Introduction: <i>Oxytropis racemosa</i> Turcz is an important minority medicine that is used mainly to improve children's indigestion, especially in inner Mongolia and Tibet. Previous studies indicated that the characteristic constituents of this plant are acylated flavonoids.<br>Objective: Rapidly identify the characteristic chemical constituents of <i>O. racemosa</i> by high-performance liquid chromatography-diode array detection-electrospray ionisation/multi-stage mass spectrometry (HPLC-DAD-ESI/MS<i><sup>n</sup></i>) and suggest a useful method to control the quality of this medicinal plant.<br>Methods: In the HPLC fingerprint, 32 flavonoids were tentatively identified by a detailed analysis of their mass spectra, UV spectra and retention times. Furthermore, 13 flavonoids were confirmed by comparison with previously isolated compounds obtained from <i>O. racemosa</i>.<br>Results: In total, 32 flavonoids, including 13 flavonoids with 3-hydroxy-3-methylglutaric acid (HMG) moieties and four flavonoids with 3-malonyl moieties, were identified in the extract of <i>O. racemosa</i>. Among the compounds identified, 10 were characterised as new compounds for their particular acylated sugar moieties.<br>Conclusions: The method described is effective for obtaining a comprehensive phytochemical profile of plants containing unstable acylated flavonoids. The method is also useful for constructing the chromatographic fingerprint of the minority medicine -<i>O. racemosa</i> Turcz for quality control. Copyright © 2012 John Wiley & Sons, Ltd.
Saussurea plants have a long history of being used for disease prevention and control in Tibetan medicine, and the species have gradually changed along with the development of history. Sausurea is mainly effective in wind-expelling, blood circulation, spasmolysis, pain relief, heat-clearing and detoxification. Characteristics, major chemical constituents and pharmacological studies of Saussurea Stella Maim. were summarized in this review based on the utilization of Sausurea medicinal plants in Tibetan areas, with the aim to provide adequate theoretical bases and references for exploring the further medicinal value and development and utilization of S. Stella. [ABSTRACT FROM AUTHOR]
Oxytropis falcata is a perennial acaulescent herb of Oxytropis leguminosae. It is an impointan traditional tibetan medicinal material of high pharmaceutical value, which grows widely in Tibet. In recent years, there has been an extensive study of this plant. This article is to summarize the knowledge of Oxytropis flacanta; its chemical composition, pharmacological and clinical application, and recommendation for furthur research.
The regulation of postprandial blood glucose (PBG) levels is an effective therapeutic method to treat diabetes and prevent diabetes-related complications. Resveratroloside is a monoglucosylated form of stilbene that is present in red wine, grapes, and several traditional medicinal plants. In our study, the effect of resveratroloside on reducing PBG was studied in vitro and in vivo. In comparison to the starch treatment alone, the oral administration of resveratroloside-starch complexes significantly inhibited the PBG increase in a dose-dependent pattern in normal and diabetic mice. The PBG level treated with resveratrol (30 mg/kg) was not lower than that of resveratroloside. Further analyses demonstrated that resveratroloside strongly and effectively inhibited α-glucosidase, with an 50% inhibitory concentration value of 22.9 ± 0.17 μM, and its inhibition was significantly stronger than those of acarbose and resveratrol (264 ± 3.27 and 108 ± 2.13 μM). Moreover, a competitive inhibition mechanism of resveratroloside on α-glucosidase was determined by enzyme kinetic assays and molecular docking experiments. The molecular docking of resveratroloside with α-glucosidase demostrated the competitive inhibitory effect of resveratroloside, which occupies the catalytic site and forms strong hydrogen bonds with the residues of α-glucosidase. Resveratrol was also determined to be a competitive inhibition mechanism on α-glucosidase by enzyme kinetic assays and molecular docking experiments. This study suggested that resveratroloside had the ability to regulate PBG levels and can be considered a potential agent for the treatment of diabetes mellitus.
ETHNOPHARMOCOLOGICAL RELEVANCE: Herbo-metallic preparations have a long history in the treatment of diseases, and are still used today for refractory diseases, as adjuncts to standard therapy, or for economic reasons in developing countries.AIM OF THE REVIEW: This review uses cinnabar (HgS) and realgar (As4S4) as mineral examples to discuss their occurrence, therapeutic use, pharmacology, toxicity in traditional medicine mixtures, and research perspectives.
MATERIALS AND METHODS: A literature search on cinnabar and realgar from PubMed, Chinese pharmacopeia, Google and other sources was carried out. Traditional medicines containing both cinnabar and realgar (An-Gong-Niu-Huang Wan, Hua-Feng-Dan); mainly cinnabar (Zhu-Sha-An-Shen Wan; Zuotai and Dangzuo), and mainly realgar (Huang-Dai Pian; Liu-Shen Wan; Niu-Huang-Jie-Du) are discussed.
RESULTS: Both cinnabar and realgar used in traditional medicines are subjected to special preparation procedures to remove impurities. Metals in these traditional medicines are in the sulfide forms which are different from environmental mercurials (HgCl2, MeHg) or arsenicals (NaAsO2, NaH2AsO4). Cinnabar and/or realgar are seldom used alone, but rather as mixtures with herbs and/or animal products in traditional medicines. Advanced technologies are now used to characterize these preparations. The bioaccessibility, absorption, distribution, metabolism and elimination of these herbo-metallic preparations are different from environmental metals. The rationale of including metals in traditional remedies and their interactions with drugs need to be justified. At higher therapeutic doses, balance of the benefits and risks is critical. Surveillance of patients using these herbo-metallic preparations is desired.
CONCLUSION: Chemical forms of mercury and arsenic are a major determinant of their disposition, efficacy and toxicity, and the use of total Hg and As alone for risk assessment of metals in traditional medicines is insufficient.
• A simultaneous microwave/ultrasonic-assisted enzymatic extraction method was established for the first time. • Simultaneous microwave/ultrasonic-assisted enzymatic process can improve antioxidant capacity of juice by-product extract. • Simultaneous microwave/ultrasonic-assisted enzymatic process can increase the extraction efficiency of antioxidant ingredients. • <b>Nitraria tangutorun</b> Bobr. juice by-products extract exhibited excellent cell protection effect from oxidative injury.<br>By-products originating from food processing are a considerable disposal problem for the food industry. Because of the absence of specifically effective processing technology, huge quantities of by-products are often abandoned as rubbish and prone to microbial spoilage. Given this, a simultaneous microwave/ultrasonic assisted enzymatic extraction (SMU-AEE) method was established for the first time, and performed for antioxidant ingredients extraction from <b>Nitraria tangutorum</b> juice by-products (NJB) in the present study. Its experimental conditions were optimized by single factor test and response surface methodology (RSM), and gave the corresponding response values for antioxidant capacity of NJB extract (NJBE) of 219.73 ± 7.03 mg TE/g, which was 27.62%-190.23% higher than those obtained by traditional extraction methods. Chemical composition assay suggested that the increasing of antioxidant capacity of NJBE by SMU-AEE was because of the improvement of extraction efficiency of antioxidant ingredients from NJB, including phenols, flavonoids and anthocyanins. Furthermore, oxidative injury protection ability assay showed that NJBE was good at protecting cells from UVB-oxidative phototoxicity and doxorubicin-oxidative cardiotoxicity, and its protecting ability surpasses or approaches to that of grape seed extract (GSE, the positive control drug), indicating its good potential to be a natural antioxidant in food and pharmaceutical industries.
• In situ derivatization-UADLLME was firstly reported for NTs in rat brain microdialysates. • Lissamine rhodamine B sulfonyl chloride was firstly used as derivatization reagent. • The method was simple, rapid, green, efficient, sensitive and low matrix effect. • This method was successfully applied for Parkinson’s rat brain microdialysates.<br>Simultaneous monitoring of several neurotransmitters (NTs) linked to Parkinson’s disease (PD) has important scientific significance for PD related pathology, pharmacology and drug screening. A new simple, fast and sensitive analytical method, based on in situ derivatization-ultrasound-assisted dispersive liquid-liquid microextraction (in situ DUADLLME) in a single step, has been proposed for the quantitative determination of catecholamines and their biosynthesis precursors and metabolites in rat brain microdialysates. The method involved the rapid injection of the mixture of low toxic bromobenzene (extractant) and acetonitrile (dispersant), which containing commercial Lissamine rhodamine B sulfonyl chloride (LRSC) as derivatization reagent, into the aqueous phase of sample and buffer, and the following in situ DUADLLME procedure. After centrifugation, 50 μL of the sedimented phase (bromobenzene) was directly injected for ultra high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) detection in multiple reaction monitoring (MRM) mode. This interesting combination brought the advantages of speediness, simpleness, low matrix effects and high sensitivity in an effective way. Parameters of in situ DUADLLME and UHPLC-MS/MS conditions were all optimized in detail. The optimum conditions of in situ DUADLLME were found to be 30 μL of microdialysates, 150 μL of acetonitrile containing LRSC, 50 μL of bromobenzene and 800 μL of NaHCO3-Na2CO3 buffer (pH 10.5) for 3.0 min at 37 °C. Under the optimized conditions, good linearity was observed with LODs (S/N > 3) and LOQs (S/N > 10) of LRSC derivatized-NTs in the range of 0.002-0.004 and 0.007-0.015 nmol/L, respectively. It also brought good precision (3.2-12.8%, peak area CVs%), accuracy (94.2-108.6%), recovery (94.5-105.5%) and stability (3.8-8.1%, peak area CVs%) results. Moreover, LRSC derivatization significantly improved chromatographic resolution and MS detection sensitivity of NTs when compared with the reported studies through the introduction of a permanent charged moiety from LRSC into NTs. Taken together, this in situ DUADLLME method was successfully applied for the simultaneous determination of six NTs in biological samples.
Recent studies on chemical constituents of Dali and their pharmacological activities were reviewed. Dali, a Tibetan medicine, consists of two Tibetan plants: Rhododendron anthopogoniodes Maxim. and R. primulaeflorum Bur. et Franch. Dali mainly contains essential oils, flavonoids and triterpenoids. The pharmacological activities of Dali are widely proved in eliminating phlegm, relieve cough and anti-asthmatic activities. As a clinical drug, it is also used for treatment of chronic bronchitis and coronary artery disease.
Four common traditional tibetan medicine prescription preparations "Anzhijinghuasan, Dangzuo, Renqingchangjue and Rannasangpei" in tibetan areas were selected as study objects in the present study. The purpose was to try to establish a kind of wet digestion and flow injection-hydride generation-atomic absorption spectrometry (FI-HAAS) associated analysis method for the content determinations of lead and arsenic in traditional tibetan medicine under optimized digestion and measurement conditions and determine their contents accurately. Under these optimum operating conditions, experimental results were as follows. The detection limits for lead and arsenic were 0.067 and 0.012 µg · mL(-1) respectively. The quantification limits for lead and arsenic were 0.22 and 0.041 µg · mL(-1) respectively. The linear ranges for lead and arsenic were 25-1,600 ng · mL(-1) (r = 0.9995) and 12.5-800 ng · mL(-1) (r = 0.9994) respectively. The degrees of precision(RSD) for lead and arsenic were 2.0% and 3.2% respectively. The recovery rates for lead and arsenic were 98.00%-99.98% and 96.67%-99.87% respectively. The content determination results of lead and arsenic in four traditional tibetan medicine prescription preparations were as fol- lows. The contents of lead and arsenic in Anzhijinghuasan are 0.63-0.67 µg · g(-1) and 0.32-0.33 µg · g(-1) in Anzhijinghua- san, 42.92-43.36 µg · g(-1) and 24.67-25.87 µg · g(-1) in Dangzuo, 1,611. 39-1,631.36 µg · g(-1) and 926.76-956.52 µg- g(-1) in Renqing Changjue, and 1,102.28-1,119.127 µg-g(-1) and 509.96-516.87 µg · g(-1) in Rannasangpei, respectively. This study established a method for content determination of lead and arsenic in traditional tibetan medicine, and determined the content levels of lead and arsenic in four tibetan medicine-prescription preparations accurately. In addition, these results also provide the basis for the safe and effective use of those medicines in clinic.
OBJECTIVE: To study the heat processing technics of Nanhanshuishi.METHOD: To find the best processing technic, the single factor experiments and orthogonal experiments were designed basing on the processing technics summarized by consulting documents, scriptures and investigating some Tibetan hospitals, meanwhile, the content of Ca, Fe, Mn, Zn, and Cu in the processed Nanhanshuishi in single factor experiments and orthogonal experiments were detected.
RESULT: The best processing technic of Nanhanshuishi was as follows: Nanhanshuishi was crashed to 10-20 mm in diameter, the ratio of the weight of Aconiti Kusnezoffii Radix and potassium nitrate was 1: 2, and the boiling time was 3 h.
CONCLUSION: The work in this article provided a basic processing technic data for clarifying the mechanism of processing and establishing the perfect processing technics of Nanhanshuishi.
Zuotai (gTso thal) is a typical representative of Tibetan medicines containing heavy metals, but there is still lack of modem safety evaluation data so far. In this study, acute toxicity test, sub-acute toxicity test, one-time administration mercury distribution experiment, long-term mercury accumulative toxicity experiment and preliminary study on clinical safety of Compound Dangzuo were conducted in the hope of obtain the medicinal safety data of Zuotai. In the acute toxicity test, half of KM mice given the lethal dose of Zuotai were not died or poisoned, and LD50 was not found. The maximum tolerated dose of Zuotai was 80 g x kg(-1). In the subacute toxicity test, Zuotai could reduce ALT, AST, Crea levels in serums under low dose (13.34 mg x kg(-1) x d(-1)) and medium dose (53.36 mg x kg(-1) x d(-1)), with significant difference under low dose, and increase the levels of ALT, AST, MDA, Crea in serums under high dose (2 000 mg x kg(-1) x d(-1)); besides, the levels of BUN and GSH in serums reduced with the increase in dose of Zuotai, indicating a significant dose-effect relationship. In the one-time administration distribution experiment, the content of mercury in rat kidney, liver and lung increased after the one-time administration with Zuotai, with a significant dose-dependent relationship in kidney. In the long-term mercury accumulative toxicity experiment, KM mice were administered with equivalent doses of Zuotai for 4.5 months and then stopped drug administration for 1.5 months. Since the 2.5th month, they showed significant mercury accumulation in kidney, which gradually reduced after drug withdrawal, without significant change in mercury content in liver, spleen and brain and ALT, AST, TBIL, BUN and Crea in serum. At the 4.5th month after drug administration, KM mice showed slight structural changes in kidney, liver and spleen tissues, and gradually recovered to normal after drug withdrawal. Besides, no significant difference in weight gain was found between the Zuotai group and the control group. According to the findings of the clinical safety study of Dangzuo, after subjects administered Dangzuo under clinical dose for one month, their serum biochemical indicators, blood routine indicators and urine routine indicators showed no significant adverse change. This study proved that traditional Tibetan medicine Zuotai was slightly toxic, with a better safety in clinical combined administration and no adverse effects on bodies under the clinical dose and clinical medication cycle. However, long-term high-dose administration of Zuotai may have a certain effect on kidney.;
The objective of the present study is to research the herb of Swertia mussotii Franch and its different extracts by tristep infrared spectroscopy. The main constitute of Swertia mussotii Franch-gentiamarin, which is also the higher content constitute, was selected as the control components to analyze the infrared spectroscopy and second derivative infrared spectroscopy of different extracts of Swertia mussotii Franch, at the same time, the different concentration of ethanol extracts were also analyzed by two-dimensional correlation spectroscopy (2D-COS). The results indicated that the intensity of 1 611 and 1 075 cm(-1) of gentiamarin, which are its two main absorptions in the infrared spectra, has the positive correlation with the content change in different extracts. The infrared spectroscopy of extracts are similar if the polarity of extract solvents is close; with the decreases in solution polarity, the intensity of 2 853, 1 733, 1 464, 1 277 and 1 161 cm(-1) in infrared spectroscopy of different extracts is increased, the content of esters and the extraction percentage terpenoid compounds are also increased; the different concentration of ethanol extracts has obviously difference when they are analyzed by two-dimensional correlation spectroscopy (2D-COS). The positive correlation between the intensity of absorptions and the content of the gentiamarin indicates that the infrared spectroscopy can reflect the content change in constitute; the similar and the change trend of the different concentrations of ethanol extract infrared spectroscopy approve the scientificalness of decoction of traditional medicine; infrared spectroscopy that used in the research can be used as an accurate, rapid and effective method in the pharmacological activity tests of transitional herbal Swertia mussotii F. and it's different extracts, even in the research on the tibetan medicine.
Four different extracts of Oxytropis falcata, including the aerial aqueous extract, and the underground aqueous extract, the aerial lipophilic extract, and the underground lipophilic extract were prepared and then administrated orally to mice at the maximum dose (50 g x kg(-1) x d(-1) calculated by raw material) for fifteen days respectively. Compared with the control group, which was administrated of 1.0% tween-80, the treatment groups did not show significant differences in appearance and behavior. However, the organcoefficient, blood biochemical indicator and pathological section results showed that the lipophilic extracts of the aerial and underground parts of O. flacata showed mild injury to the liver of mice, while the aerial and underground aqueous extracts and the underground lipophilic extract showed mild toxicity to the kidney of male mice. Chemical analysis showed that the lipophilic extracts of the aerial and underground parts, especially aerial lipophilic extract, consisted of large amount of flavonoid aglycones with little amount of polysaccharides and proteins, while the aqueous extracts contained much polysaccharides and proteins with almost no flavonoid aglycones detected.
Tai Chi Chuan (TCC) practice is currently intentionally applied in clinical populations, especially those with cardiovascular diseases because of its potential benefits on the autonomic nervous system. The long-term effect of TCC practice on heart rate variability (HRV) remains largely unknown. In this study, we recruited 23 TCC practitioners whose experience averaged approximately 21 years and 19 controls matched by age, sex and education to examine the effect of TCC practice on the autonomic nervous system during a resting state and during an abdominal breathing state. HRV was measured by traditional electrocardiogram (ECG) recording. The results showed that the low frequency, total power frequency, and normalized low frequency components and the low-frequency/high-frequency ratio were significantly higher, whereas the normalized high frequency was significantly lower in the TCC practitioners relative to controls during the abdominal breathing state. However, we did not detect any significant difference in the HRV measures during the resting state between the two groups. Additionally, TCC experience did not correlate with HRV components either in the abdominal state or the resting state in the TCC group. Considering all of these findings, we suggest that TCC improves vagal activity and the balance between sympathetic and parasympathetic activity during the relaxation state. This study also provides direct physiological evidence for the role of TCC practice in relaxation.
Zuotai is composed mainly of β-HgS, while cinnabar mainly contains α-HgS. Both forms of HgS are used in traditional medicines and their safety is of concern. This study aimed to compare the hepatotoxicity potential of Zuotai and α-HgS with mercury chloride (HgCl2) and methylmercury (MeHg) in mice. Mice were orally administrated with Zuotai (30 mg/kg), α-HgS (HgS, 30 mg/kg), HgCl2 (33.6 mg/kg), or CH3HgCl (3.1 mg/kg) for 7 days, and liver injury and gene expressions related to toxicity, inflammation and Nrf2 were examined. Animal body weights were decreased by HgCl2 and to a less extent by MeHg. HgCl2 and MeHg produced spotted hepatocyte swelling and inflammation, while such lesions are mild in Zuotai and HgS-treated mice. Liver Hg contents reached 45-70 ng/mg in HgCl2 and MeHg groups; but only 1-2 ng/mg in Zuotai and HgS groups. HgCl2 and MeHg increased the expression of liver injury biomarker genes metallothionein-1 (MT-1) and heme oxygenase-1 (HO-1); the inflammation biomarkers early growth response gene (Egr1), glutathione S-transferase (Gst-mu), chemokine (mKC) and microphage inflammatory protein (MIP-2), while these changes were insignificant in Zuotai and HgS groups. However, all mercury compounds were able to increase the Nrf2 pathway genesNAD(P)H: quinone oxidoreductase 1 (Nqo1) and Glutamate-cysteine ligase, catalytic subunit (Gclc). In conclusion, the Tibetan medicine Zuotai and HgS are less hepatotoxic than HgCl2 and MeHg, and differ from HgCl2 and MeHg in hepatic Hg accumulation and toxicological responses.
UNLABELLED: Zuotai is composed mainly of β-HgS, while cinnabar mainly contains α-HgS. Both forms of HgS are used in traditional medicines and their safety is of concern. This study aimed to compare the hepatotoxicity potential of Zuotai and α-HgS with mercury chloride (HgCl2) and methylmercury (MeHg) in mice. Mice were orally administrated with Zuotai (30 mg/kg), α-HgS (HgS, 30 mg/kg), HgCl2 (33.6 mg/kg), or CH3HgCl (3.1 mg/kg) for 7 days, and liver injury and gene expressions related to toxicity, inflammation and Nrf2 were examined. Animal body weights were decreased by HgCl2 and to a less extent by MeHg. HgCl2 and MeHg produced spotted hepatocyte swelling and inflammation, while such lesions are mild in Zuotai and HgS-treated mice. Liver Hg contents reached 45-70 ng/mg in HgCl2 and MeHg groups; but only 1-2 ng/mg in Zuotai and HgS groups. HgCl2 and MeHg increased the expression of liver injury biomarker genes metallothionein-1 (MT-1) and heme oxygenase-1 (HO-1); the inflammation biomarkers early growth response gene (Egr1), glutathione S-transferase (Gst-mu), chemokine (mKC) and microphage inflammatory protein (MIP-2), while these changes were insignificant in Zuotai and HgS groups. However, all mercury compounds were able to increase the Nrf2 pathway genes NAD(P)H: quinone oxidoreductase 1 (Nqo1) and Glutamate-cysteine ligase, catalytic subunit (Gclc). In conclusion, the Tibetan medicine Zuotai and HgS are less hepatotoxic than HgCl2 and MeHg, and differ from HgCl2 and MeHg in hepatic Hg accumulation and toxicological responses.
Background. The circadian clock is involved in drug metabolism, efficacy and toxicity. Drugs could in turn affect the biological clock as a mechanism of their actions. Zuotai is an essential component of many popular Tibetan medicines for sedation, tranquil and "detoxification," and is mainly composed of metacinnabar (β-HgS). The pharmacological and/or toxicological basis of its action is unknown. This study aimed to examine the effect of Zuotai on biological clock gene expression in the liver of mice. Materials and methods. Mice were orally given Zuotai (10 mg/kg, 1.5-fold of clinical dose) daily for 7 days, and livers were collected every 4 h during the 24 h period. Total RNA was extracted and subjected to real-time RT-PCR analysis of circadian clock gene expression. Results. Zuotai decreased the oscillation amplitude of the clock core gene Clock, neuronal PAS domain protein 2 (Npas2), Brain and muscle Arnt-like protein-1 (Bmal1) at 10:00. For the clock feedback negative control genes, Zuotai had no effect on the oscillation of the clock gene Cryptochrome (Cry1) and Period genes (Per1-3). For the clock-driven target genes, Zuotai increased the oscillation amplitude of the PAR-bZip family member D-box-binding protein (Dbp), decreased nuclear factor interleukin 3 (Nfil3) at 10:00, but had no effect on thyrotroph embryonic factor (Tef); Zuotai increased the expression of nuclear receptor Rev-Erbα (Nr1d1) at 18:00, but had little influence on the nuclear receptor Rev-Erbβ (Nr1d2) and RORα. Conclusion. The Tibetan medicine Zuotai could influence the expression of clock genes, which could contribute to pharmacological and/or toxicological effects of Zuotai.
Background. The circadian clock is involved in drug metabolism, efficacy and toxicity. Drugs could in turn affect the biological clock as a mechanism of their actions. Zuotai is an essential component of many popular Tibetan medicines for sedation, tranquil and "detoxification," and is mainly composed of metacinnabar (β-HgS). The pharmacological and/or toxicological basis of its action is unknown. This study aimed to examine the effect of Zuotai on biological clock gene expression in the liver of mice. Materials and methods. Mice were orally given Zuotai (10 mg/kg, 1.5-fold of clinical dose) daily for 7 days, and livers were collected every 4 h during the 24 h period. Total RNA was extracted and subjected to real-time RT-PCR analysis of circadian clock gene expression. Results. Zuotai decreased the oscillation amplitude of the clock core gene Clock, neuronal PAS domain protein 2 (Npas2), Brain and muscle Arnt-like protein-1 (Bmal1) at 10:00. For the clock feedback negative control genes, Zuotai had no effect on the oscillation of the clock gene Cryptochrome (Cry1) and Period genes (Per1-3). For the clock-driven target genes, Zuotai increased the oscillation amplitude of the PAR-bZip family member D-box-binding protein (Dbp), decreased nuclear factor interleukin 3 (Nfil3) at 10:00, but had no effect on thyrotroph embryonic factor (Tef); Zuotai increased the expression of nuclear receptor Rev-Erbα (Nr1d1) at 18:00, but had little influence on the nuclear receptor Rev-Erbβ (Nr1d2) and RORα. Conclusion. The Tibetan medicine Zuotai could influence the expression of clock genes, which could contribute to pharmacological and/or toxicological effects of Zuotai.
As a form of traditional, complementary, and alternative medicine (TCAM), traditional Tibetan medicine has developed into a mainstay of medical care in Tibet and has spread from there to China and then to the rest of the world. Thus far, research on traditional Tibetan medicine has focused on the study of the plant and animal sources of traditional medicines, study of the histology of those plants and animals, chemical analysis of traditional medicines, pharmacological study of those medicines, and evaluation of the clinical efficacy of those medicines. A number of papers on traditional Tibetan medicines have been published, providing some evidence of the efficacy of traditional Tibetan medicine. However, many traditional Tibetan medicines have unknown active ingredients, hampering the establishment of drug quality standards, the development of new medicines, commercial production of medicines, and market availability of those medicines. Traditional Tibetan medicine must take several steps to modernize and spread to the rest of the world: the pharmacodynamics of traditional Tibetan medicines need to be determined, the clinical efficacy of those medicines needs to be verified, criteria to evaluate the efficacy of those medicines need to be established in order to guide their clinical use, and efficacious medicines need to be acknowledged by the pharmaceutical market. The components of traditional Tibetan medicine should be studied, traditional Tibetan medicines should be screened for their active ingredients, and techniques should be devised to prepare and manufacture those medicines.
Abstract Ethnopharmacological relevance Tibetan medicine has been practiced for 3800 years. Anzhijinhua San (AZJHS), which is a traditional Tibetan medicine, has been effective in the treatment of indigestion, anorexia and cold diarrhea. However, the effects of AZJHS on allergic diarrhea have not been reported. Aim of the study The aim of the present study was to elucidate the effect of AZJHS on experimental ovalbumin-induced diarrhea and elucidate its possible mechanism. Materials and methods Female BALB/c mice were sensitized by intraperitoneal injection with 50 μg ovalbumin (OVA) and 1 mg alum in saline twice during a 2-week period. From day 28, mice were orally challenged with OVA (50 mg) every other day for a total of ten times. AZJHS (46.8 and 468.0 mg/kg) was orally administered every other day from day 0–46. Food allergy symptoms were evaluated. OVA- specific IgE, 5-HT and its metabolites in serum were determined. Immunohistochemical and histopathology were performed in gastrointestinal tract tissues. 5-HT-related gene expression was assayed in the colon. Results Severe symptoms of allergic diarrhea were observed in the model group (diarrhea, anaphylactic response, and rectal temperature). AZJHS (46.8 and 468.0 mg/kg) significantly reduced mouse diarrhea and significantly prevented the increases in OVA-specific IgE levels (P < 0.05), which challenge with OVA. AZJHS (46.8 and 468.0 mg/kg) significantly prevented the increases in 5-HT-positive cells. The nuclei of EC cells in the AZJHS (46.8 and 468.0 mg/kg) group increased in size and the secretory granules were fewer in number compared with those in the model group. AZJHS (46.8 and 468.0 mg/kg) significantly increased the relative fold changes of 5-HTP and 5-HT compared with the model group. The mRNA expression of the serotonin transporter (Sert) and serotonin receptor 3A (Htr3a) was significantly decreased after the 10th challenge with OVA, and AZJHS (46.8 and 468.0 mg/kg) significantly increased these levels. Conclusions We demonstrated that the administration of AZJHS attenuated OVA-induced diarrhea by regulating the serotonin pathway. These results indicated that AZJHS may be a potential candidate as an anti-allergic diarrhea agent. Graphical abstract fx1 [ABSTRACT FROM AUTHOR]
Pages |