To explore the medication regularity of Tibetan medicine in the treatment of spleen and stomach diseases, analyze the potential drug targets and interactions of the prescriptions, and reveal the mechanism of Tibetan medicine in the treatment of spleen and stomach diseases. The prescriptions in Tibetan medicine for treatment of spleen and stomach diseases were collected, and Traditional Chinese Medicine Inheritance Support System (TCMISS) was used to analyze the association rules between the herbs and discover the core herbs and new prescriptions. The integrated pharmacology platform V1.0 software was used to construct "herb-compound-target" network and investigate the interactions between various herbs and related pathways of Tibetan medicine Wuwei Shiliu powder in the treatment of spleen and stomach diseases. Among the 216 prescriptions of Tibetan medicine in the treatment of spleen and stomach diseases, pomegranate seed was used at a highest frequency (118 times), followed by white cardamom (107 times) and comatose (107 times). 12 new prescriptions were evolved by using the association rules (support>=34%, confidence>=0.85). 5 242 related drug targets and 20 related pathways were obtained from classic formula Wuwei Shiliu Powder (FDR<0.01). It was proposed that Tibetan medicine treatment for spleen and stomach diseases was mainly based on proliferation of "stomach fire" and the main drugs were for regulating Qi-flowing for strengthening spleen. The mechanism may be associated with regulation of digestive juice secretion, proton pump, mitochondria, regulation of intestinal digestion and immunity, the body's immunity to microorganisms function and other multiple targets and pathways to achieve the joint intervention.
OBJECTIVES: The hepatoprotective effect of Gentianae macrophyllae root extract (GME) on alcoholic liver disease (ALD) was evaluated through ethanol induced ALD animal model.METHODS: Mice were randomly divided into control normal group (10 mice), ethanol-induced ALD model group (10 mice) and GME plus ethanol group (30 mice). Mice in model group were given intragastric administration with 50% (v/v) ethanol aqueous solution (200 μl for each) once daily for 19 days. Mice in control normal group received equal volumes of water. Mice in GME plus ethanol group were given intragastric administration with 50% (v/v) ethanol aqueous solution (200 μl for each) once daily at 10:00 a.m., after 1 h, mice in GME group sequentially were treated with 20, 40 and 100 mg/kg of GME by gastric gavage for 19 days. the average food and water consumed by the mice in every group were recorded every 2 days and body weight of every mouse in every group was measured every 2 days.
KEY FINDINGS: Results showed that GME significantly improved alcohol induced liver injury in a dose-dependent manner. The impaired hepatic tissue structure was repaired and the collagen deposition declined after GME administration. Meanwhile, the level of malonaldehyde (MDA), Aspartate transaminase (AST) and alanine transaminase (ALT) (indicators of liver damage) in blood serum were significantly controlled by GME with a dose-dependent manner, moreover, body weight and liver index were also improved after administration of GME. Pro-inflammatory cytokines including MCP-1, TNF-α, IL-1 and IL-6 were detected through RT-PCR and ELISA in experiment and GME can significantly inhibit the expression of TNF-α, IL-1 and IL-6 but have no effect on MCP-1. In order to explore the mechanism of GME on ALD, MAPKs pathway was examined and results indicated that GME attenuated ALD through inhibiting the phosphorylation of JNK and P38 and further suppressing the initiation of inflammation.
CONCLUSIONS: GME attenuated ALD through inhibiting the phosphorylation of JNK and P38 and further suppressing the initiation of inflammation.
BACKGROUND: In previous investigation, we have identified antioxidative effects of water-soluble ethanolic extracts (named as AKE) from Arenaria kansuensis and inferred that these extracts or their constituents may also have antihypoxic activity. A. kansuensis has been widely used in traditional Tibetan medicine for altitude sickness (AS) and has been known as the herb of anti-inflammatory and hypoxia resistance for a long time.PURPOSE: The purpose of this study is to evaluate protective effects of AKE and its major constituents against hypoxia-induced lethality in mice and RSC96 cells.
STUDY DESIGN AND METHODS: Hypoxia-induced lethality in mice was investigated by 3 experimental animal models of hypoxia. Meanwhile, we established a RSC96 cell model of hypoxia which applied to screen and assess the anti-hypoxic activity of compounds isolated from A. kansuensis.
RESULTS: Results indicated that AKE dose-dependently prolonged survival time of hypoxia induced lethality in mice compared to vehicle group and exhibited significantly anti-hypoxic effect. AKE also enhanced the number of red blood cells (RBC) and the concentration of hemoglobin (HB). 8 compounds were bio-guided separated and purified from AKE based on the animal model and cell model of hypoxia. Among which pyrocatechol (C16) and tricin 7-O-β-d-glucopyranoside (C13) were confirmed to express better protective effects on cell damage induced by hypoxia, suggesting that these two compounds are major active constituents of AKE for anti-hypoxia.
CONCLUSION: This study demonstrated that pyrocatechol and tricin 7-O-β-d-glucopyranoside could be therapeutic candidates for treatment of AS. It is the first time to find the major active constituents of AKE for anti-hypoxia. Meanwhile, a RSC96 cell model of hypoxia was established to screen anti-hypoxic activity of compounds for the first time.
Background: Hypecoum leptocarpum Hook. f. et Thoms., which is used in traditional Tibetan medicine as an antipyretic, antitussive, analgesic, and anti-inflammatory agent, contains a variety of alkaloids that could be responsible for its analgesic and anti-inflammatory properties. Objective: The present study was designed to investigate the anti-inflammatory activity of the total alkaloids from H. leptocarpum (AHL) in vitro and to elucidate the chemical structure of the anti-inflammatory components in AHL. Materials and Methods: Chemical characterization was performed using liquid chromatography/quadrupole-time-of-flight mass and diode-array detector-high performance liquid chromatography. The anti-inflammatory effects of AHL were investigated by measuring the production of inflammatory cytokines using enzyme-linked immunosorbent assay and mRNA expression by real-time polymerase chain reaction in lipopolysaccharide-induced RAW 264.7 macrophages. Results: Chemical analysis of AHL revealed the presence of seven alkaloids, protopine (13.3%), cryptopine (1.5%), leptopidinine, leptocarpine, corydamine, dihydroleptopine, and oxohydrastinine. AHL significantly suppressed the production of nitric oxide (NO), interleukin-1 beta (IL-1 β), IL-6, and tumor necrosis factor-alpha (TNF-α) in LPS-induced RAW 264.7 cells. The maximum levels of suppression of NO, IL-1 β, IL-6, and TNF-α were 86.8% ± 2.2%, 70.1% ± 1.5%, 100.1% ± 2.5%, and 50.8% ± 3.6%, respectively. IC50values of suppression of cytokine production by AHL were 7.47 ± 2.81 μg/mL (NO), 0.12 ± 0.28 μg/mL (IL-1 β), 0.56 ± 0.37 μg/mL (IL-6), and 18.95 ± 5.23 μg/mL (TNF-α). AHL was also shown to downregulate mRNA expression of inducible NO synthase, IL-1 β, IL-6, and TNF-α in vitro. Conclusion: The study provides convincing evidence that AHL has strong anti-inflammatory activity. The potent activity is likely a result of synergy between the different alkaloids. Abbreviations used: The total alkaloids from H. leptocarpum: AHL; Nitric oxide: NO; Interleukin-1 beta IL-1β; Interleukin-6: IL-6; Tumor necrosis factor-alpha: TNF-α; Prostaglandin E2: PGE2; Inducible nitric oxide synthase: iNOS; Nonsteroidal anti-inflammatory drugs: NSAIDs; lipopolysaccharide: LPS; The total ion chromatograms: TIC; The liquid chromatography/quadrupole-time of flight: LC/Q-TOF; Nuclear factor-kappa B: NF-κB; Janus kinase-signal transducers and activators of transcription: JAK-STAT. [ABSTRACT FROM AUTHOR]
OBJECTIVE: To study the chemical constituents of Arenaria kansuensis.METHOD: Column chromatographic techniques were applied to isolated constituents. A combination of physico-chemical properties and spectroscopic analysis were used to identify structures of constituents.
RESULT: Five compounds were obtained and elucidated as tricin (1), tricin-7-O-beta-D-glucopyranoside (2), tricin 4'-O-beta-guaiacylglyceryl ether (3), isoscoparin (4) and isovitexin (5).
CONCLUSION: Compound 2, 3 and 5 were isolated from A. kansuensis for the first time, compound 3 was obtained from the family Caryophyllaceae for the first time.
Fecal Tibetan medicines have a long history of application in China, with a good clinical efficacy. In order to promote the development and modernization of these medicines, we consulted ancient and modern Tibetan medicine literatures to collect and summarize the names, original species, natures, flavor, functions and processing methods of fecal Tibetan medicines. A total of 35 fecal Tibetan medicines were collected, such as Jiufen, Heibingpian, Langfen, Mafen, Goufen, Gezifen. The most commonly used medicines were Jiufen and Heibingpian. Both were mainly used for the treatment of indigestion, food abdominal distension, gastric ulcer, and other gastrointestinal diseases. At present, there are only a few studies on the active ingredients, pharmacodynamics and mechanism of action of these medicines. Therefore, further study shall be conducted. The regulation of gut microbiota may be a new way to evaluate the effectiveness of fecal Tibetan medicines and their mechanism of action.
To achieve a high yield of tropane alkaloids (TA) and exploit the alpine plant sustainably, an optimized protocol for induction and establishment of hairy roots culture of <i>Prezwalskia tangutica</i> Maxim was developed through selection of appropriate <i>Agrobacterium</i> strain and the explant type. The hypocotyl is more readily facile to induce the HR than the cotyledon is when infected with the three different agrobacterium strains. MUS440 has an efficiency (of up to 20%), whereas the ATCC10060 (A4) can induce HR on both types of explants with the highest frequency (33.33%), root length (21.17 ± 2.84 cm), and root number (10.83 ± 1.43) per explant than the other strains. The highest HR production resulted from using hypocotyl as explants. Independent transformed HR was able to grow vigorously and to propagate on a no-hormone 1/2MS liquid medium. The presence of pRi <i>rol</i>B gene in transformation of HR was confirmed by PCR amplification. In the liquid medium, the HR growth curve appeared to be “S” shaped, and ADB had increased to 4.633 g/l. Moreover, HPLC analysis showed that HR lines have an extraordinary ability to produce atropine (229.88 mg/100 g), anisodine (4.09 mg/100 g), anisodamine (12.85 mg/100 g), and scopolamine (10.69 mg/100 g), which were all more significant than the control roots. In conclusion, our study optimized the culture condition and established a feasible genetics reactor for <i>P. tangutica</i> green exploration and biological study in the alpine region.
Background Individuals have increasingly sought complementary therapies to enhance health and well-being during cancer, although little evidence of their effect is available. Objectives We investigated how an Iyengar yoga program affects the self-identified worst symptom in a group of participants. whether quality of life, spiritual well-being, and mood disturbance change over the Iyengar yoga program and at 6 weeks after the program. how, from a participant's perspective, the Iyengar yoga program complements conventional cancer treatment. Patients and Methods This pre-post instrumental collective case study used a mixed methods design and was conducted at a private Iyengar yoga studio. The sample consisted of 24 volunteers (23 women, 1 man; 88% Caucasian; mean age: 49 years) who were currently on treatment or who had been treated for cancer within the previous 6 months, and who participated in ten 90-minute weekly Iyengar yoga classes. The main outcome measures were most-bothersome symptom (Measure Your Medical Outcome Profile 2 instrument), quality of life and spiritual well-being (Functional Assessment of Chronic Illness Therapy-General subscale and Spiritual subscale), and mood disturbance (Profile of Mood States-Short Form). Participant perspectives were obtained in qualitative interviews. Results Statistically significant improvements were reported in most-bothersome symptom (t((23)) = 5.242; p< 0.001), quality of life (F-(2,F-46) = 14.5; p<0.001), spiritual well-being (F-(2,F-46) = 14.4; p<0.001), and mood disturbance (F-(2,F-46) = 10.8; p<0.001) during the program. At follow-up, quality of life (t((21)) = -3.7; p = 0.001) and mood disturbance (t((21)) = 2.4; p = 0.025) significantly improved over time. Categorical aggregation of the interview data showed that participants felt the program provided them with various benefits not included on the outcomes questionnaires. Conclusions Over the course of the Iyengar Yoga for Cancer program, participants reported an improvement in overall well-being. The program was also found to present participants with a holistic approach to care and to provide tools to effectively manage the demands of living with cancer and its treatment.
Liver disease is one of the most risk factors threatening human health. It is of great significance to find drugs that can treat liver diseases, especially for acute and chronic hepatitis, non-alcoholic fatty liver disease, and liver cancer. The search for drugs with good efficacy from traditional natural medicines has attracted more and more attention. Tibetan medicine, one of the China's traditional medical systems, has been widely used by the Tibetan people for the prevention and treatment of liver diseases for hundreds of years. The present paper summarized the natural Tibetan medicines that have been used in Tibetan traditional system of medicine to treat liver diseases by bibliographic investigation of 22 Tibetan medicine monographs and drug standards. One hundred and ninety three species including 181 plants, 7 animals, and 5 minerals were found to treat liver diseases in traditional Tibetan medicine system. The most frequently used species are Carthamus tinctorius, Brag-zhun, Swertia chirayita, Swertia mussotii, Halenia elliptica, Herpetospermum pedunculosum, and Phyllanthus emblica. Their names, families, medicinal parts, traditional uses, phytochemicals information, and pharmacological activities were described in detail. These natural medicines might be a valuable gift from the old Tibetan medicine to the world, and would be potential drug candidates for the treatment of liver diseases. Further studies are needed to prove their medicinal values in liver diseases treatment, identify bioactive compounds, elucidate the underlying mechanism of action, and clarify their side effects or toxicity with the help of modern phytochemical, pharmacological, metabonomics, and/or clinical trial methods.
Graphical abstract: <br>Display Omitted<br>Highlights: ► <b>Ligularia achyrotricha</b> is a traditional Tibetan medicine. ► Ligulachyroine A, a new alkaloid was isolated from the roots of <b>L. achyrotricha</b>. ► Eleven known compounds were also isolated from this species. ► Ligulachyroine A exhibited moderate activity against HL-60 and SMMC-7721 cells.<br><b>Ligularia achyrotricha</b> (Diels) Ling has been used as a traditional Tibetan herbal medicine. Ligulachyroine A (<b>1</b>), a new twelve-membered macrocyclic pyrrolizidine alkaloid with a ketonic group located at C-3 and an hydroxy group linked at C-8, was isolated from the roots of <b>L</b>. <b>achyrotricha</b>. It is particularly noteworthy that the structure of <b>1</b> rarely appears in any other naturally occurring twelve-membered macrocyclic pyrrolizidine alkaloid reported to date. Three known lignans (<b>2</b>-<b>4</b>) and eight known coniferyl and sinapyl alcohol derivatives (<b>5</b>-<b>12</b>) were also obtained in this species. Their structures were elucidated through a careful analysis of their IR, MS, and NMR spectra. Compound <b>1</b> exhibited moderate activity against HL-60 and SMMC-7721 cells.
Traditional Tibetan medicine provides an abundant source of knowledge on human ailments and their treatment. As such, it is necessary to explore their active single compounds used to treat these ailments to discover lead compounds with good pharmacologic properties. In this present work, animal medicine, Osteon Myospalacem Baileyi extracts have been separated using a two-dimensional preparative chromatographic method to obtain single compounds with high purity as part of the following pharmacological research. Five high-purity cyclic dipeptides from chromatography work were studied for their dihydroorotate dehydrogenase inhibitory activity on recombinant human dihydroorotate dehydrogenase enzyme and compound Fr. 1-4 was found to contain satisfying inhibition activity. The molecular modeling study suggests that the active compound Fr. 1-4 may have a teriflunomide-like binding mode. Then, the energy decomposition study suggests that the hydrogen bond between Fr. 1-4 and Arg136 can improve the binding mode to indirectly increase the van der Waals binding energy. All the results above together come to the conclusion that the 2, 5-diketopiperazine structure group can interact with the polar residues well in the active pocket using electrostatic power. If some proper hydrophobic groups can be added to the sides of the 2, 5-diketopiperazine group, it is believed that better 2, 5-diketopiperazine dihydroorotate dehydrogenase inhibitors will be found in the future.
Animal medicine is an important part in traditional Tibetan medicine. However, information about the chemical composition of animal medicine is very limited, and there is a lack of comprehensive chromatographic purification methods. In the present work, animal medicine Osteon Myospalacem Baileyi was taken as an example and a novel two-dimensional preparative chromatographic method was established for the preparation of single compounds with high purity from the extract of Osteon Myospalacem Baileyi. The first-dimension preparation was carried on a DAISO Silica prep column, and ten fractions were obtained from the 112.3 g crude sample within 12 injections. A diol prep column used in nonaqueous mobile phase was selected for the second-dimension preparation. The purity of the compounds isolated from the crude extract was >98%, which indicated that the method built in this work was efficient to manufacture single compounds of high purity from the extract of Osteon Myospalacem Baileyi. Additionally, this method showed great potential in the purification of weakly polar chemicals and it could act as a good example in the purification of other traditional animal medicines.
Gentiana straminea is a popular Tibetan medicine that has been used for thousands of years in China to treat various diseases and conditions. Although it has multiple pharmaceutical purposes and important economic plant resource in China, transcriptome and molecular base still known limited. In flowering season, samples were collected from different tissues, using the NGS Illumina. Solexa platform, about 58.85 million sequencing reads were generated and assembled de novo, yielding 78,764 high quality unigenes with an average length of 1090bp. Gene Ontology (GO), KEGG pathway mapping showed that 49,033 of these were identified as putative homologs of annotated sequences in the protein databases. Among them, candidate genes associated with iridoid, flavonoid and anthocyanin were identified. Further the key enzymes involved to iridoid and flavonoid synthesis pathway were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) on different tissues, the flower and root had the higher expression than leaves. In addition, 7591 SSR markers were identified from the unigenes of the G. straminea transcriptome. The foundation of G. straminea provided the important resource for facilitating to study molecular and functional genomics of it and related this species on the Qinghai-Tibet Plateau.
Gentiana straminea is a popular Tibetan medicine that has been used for thousands of years in China to treat various diseases and conditions. Although it has multiple pharmaceutical purposes and important economic plant resource in China, transcriptome and molecular base still known limited. In flowering season, samples were collected from different tissues, using the NGS Illumina. Solexa platform, about 58.85 million sequencing reads were generated and assembled de novo, yielding 78,764 high quality unigenes with an average length of 1090bp. Gene Ontology (GO), KEGG pathway mapping showed that 49,033 of these were identified as putative homologs of annotated sequences in the protein databases. Among them, candidate genes associated with iridoid, flavonoid and anthocyanin were identified. Further the key enzymes involved to iridoid and flavonoid synthesis pathway were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) on different tissues, the flower and root had the higher expression than leaves. In addition, 7591 SSR markers were identified from the unigenes of the G. straminea transcriptome. The foundation of G. straminea provided the important resource for facilitating to study molecular and functional genomics of it and related this species on the Qinghai-Tibet Plateau.
Dynamic microwave-assisted extraction (DMAE) technique was employed for the extraction of polysaccharides from Lycium ruthenicum (LRP). The extracting parameters were optimized by using three-variable-three-level Box-Behnken design and response surface methodology (RSM) based on the single-factor experiments. RSM analysis indicated good correspondence between experimental and predicted values. The optimum extraction parameters for the yield of polysaccharide were ratio of water to raw material 31.5 mL/g, extracting time 25.8 min and microwave power 544.0 W. Polysaccharide was analyzed by chemical methods and Fourier-transform infrared (FT-IR). The antioxidant activities of LRP were investigated including scavenging activity of 2,2-diphenyl-1-picrylhydrazyl (DPPH), hydrogen peroxide and free radicals of superoxide anion in vitro. The results of antioxidant activity exhibited LRP had the potential to be explored as novel natural antioxidant for using in functional foods or medicine.
ETHNOPHARMACOLOGICAL RELEVANCE: Osteon Myospalacem Baileyi, known as Sai long gu (Tibetan language, means "blind rat bone"), is the whole skeleton of Tibet plateau rodentia animal Myospalacem Baileyi. Osteon Myospalacem Baileyi had been widely used in the Tibet region as an anti-osteoporosis drug and since 1991 Osteon Myospalacem Baileyi has been listed in the Pharmacopoeia of People's Republic of China as the first-class animal new medical material. However, the mechanism of its anti-osteoporosis activities is still unclear. It is very desirable to solve this problem for further study.MATERIALS AND METHODS: in this study, preparative chromatography was employed to produce the active fraction ET4 from Osteon Myospalacem Baileyi crude. Flow cytometry and MTT assay were used to evaluate the toxicities of ET4. BMM cells were separated from mouse bone marrow to test the inhibition effects of ET4 on osteoclastogenesis. Western blot was used to find out the pathways, through which ET4 could act on osteoclastogenesis. Q-PCR was used to test the osteoclastogenesis marker genes. At last, immunofluorescence confocal microscopy was used to test the osteoclastogenesis master protein NFATc1 nuclei translocation.
RESULTS: In this study we report that ET4, at the dose of 60μg/mL, significantly inhibited the formation of osteoclasts. Notably, ET4 did not affect the BMM viability at that dose. In addition, Osteon Myospalacem Baileyi could inhibit the expression of osteoclast marker genes, including cathepsin K (CTSK), nuclear factor of activated T cells cytoplasmic 1 (NFATc1), tartrate resistant acid phosphatase (TRAP, Acp5) dendrite cell-specific transmembrane protein (DC-STAMP), calcitonin receptor (CTR), osteoclast associated and immunoglobulin-like receptor (OSCAR). Mechanistically, ET4 dose- and time-dependently blocked the RANKL-induced activation of ERK and c-Fos as well as the induction of NFATc1 which is essential for OC formation.
CONCLUSIONS: These data suggest that ET4 might be a useful alternative therapy in preventing or treating osteolytic diseases.
ObjectivesSubsyndromal depression (SSD) and subsyndromal anxiety (SSA) are common in the elderly and if left untreated, contributes to a lower quality of life, increased suicide risk, disability and inappropriate use of medical services. Innovative approaches are necessary to address this public health concern. We evaluate a community‐based psychosocial intervention program and its effect on mental health outcomes in Singaporean older adults.
Method
Elderly participants with SSD and SSA, as assessed on the Geriatric Depression Scale and Geriatric Anxiety Inventory, were included. Intervention groups include Tai Chi exercise, Art Therapy, Mindfulness Awareness Practice and Music Reminiscence Therapy. The program was divided into a single intervention phase and a combination intervention phase. Outcomes were measured with the Zung Self‐Rating Depression Scale (SDS) and Zung Self‐Rating Anxiety Scale (SAS) at baseline, 4 weeks, 10 weeks, 24 weeks and 52 weeks. The program had ethics board approval.
Results
A hundred and one subjects (25 males, 76 females; mean age = 71 years, SD = 5.95) participated. There were significant reductions in SDS and SAS scores in the single intervention phase (P < 0.05), and these reductions remained significant at week 52, after completion of the combination intervention phase, relative to baseline (P < 0.001).
Conclusion
Participating in these psychosocial interventions led to a positive improvement in SSD and SSA symptoms in these elderly subjects over a year. This simple, inexpensive and culturally acceptable approach should be adequately studied and replicated in other communities.
Amyloid-beta peptide is central to the pathology of Alzheimer's disease, because it is neurotoxic—directly by inducing oxidant stress, and indirectly by activating microglia. A specific cell-surface acceptor site that could focus its effects on target cells has been postulated but not identified. Here we present evidence that the 'receptor for advanced glycation end products' (RAGE) is such a receptor, and that it mediates effects of the peptide on neurons and microglia. Increased expression of RAGE in Alzheimer's disease brain indicates that it is relevant to the pathogenesis of neuronal dysfunction and death.
Pages |