Compatibility of Polygonati Rhizoma and Angelicae Sinensis Radix enhance the alleviation of metabolic dysfunction-associated fatty liver disease by promoting fatty acid ß-oxidation.

Jiuzhuan Huangjing Pills (JHP) composed of Polygonati Rhizoma (PR) and Angelicae Sinensis Radix (ASR) remedied mitochondria to cure metabolic dysfunction-associated fatty liver disease (MAFLD). However, a comparison of the anti-MAFLD ability between JHP prescription and PR and ASR single-medicines in MAFLD has not been performed, and the action mechanisms and substances remain unknown. Our results show that JHP, PR and ASR decreased serum and liver lipid levels. The effects of JHP were stronger than those of PR and ASR. JHP, PR and ASR afforded protection to mitochondrial ultrastructure, and regulated oxidative stress and energy metabolism in mitochondria. JHP also regulated the expression of ß-oxidation genes, which were not regulated by PR and ASR. JHP-, PR- and ASR-derived components in mitochondrial extracts regulated oxidative stress, energy metabolism, and ß-oxidation gene expression and alleviated cellular steatosis. Four, six and eleven compounds were identified in mitochondrial extracts from PR-, ASR- and JHP-treated rats, respectively. The data suggest that JHP, PR and ASR alleviated MAFLD by remedying mitochondria, while the ability of JHP was stronger than that of PR and ASR, which was involved with the ß-oxidation promotion. The compounds identified may be the main ingredients in the three extracts active in MAFLD improvement.

The Impact of Traditional Chinese Medicine on Mitophagy in Disease Models.

Mitophagy plays an important role in maintaining mitochondrial quality and cell homeostasis through the degradation of damaged, aged, and dysfunctional mitochondria and misfolded proteins. Many human diseases, particularly neurodegenerative diseases, are related to disorders of mitochondrial phagocytosis. Exploring the regulatory mechanisms of mitophagy is of great significance for revealing the molecular mechanisms underlying the related diseases. Herein, we summarize the major mechanisms of mitophagy, the relationship of mitophagy with human diseases, and the role of traditional Chinese medicine (TCM) in mitophagy. These discussions enhance our knowledge of mitophagy and its potential therapeutic targets using TCM.

Targeting PINK1 Using Natural Products for the Treatment of Human Diseases.

PINK1, also known as PARK6, is a PTEN-induced putative kinase 1 that is encoded by nuclear genes. PINK1 is ubiquitously expressed and regulates mitochondrial function and mitophagy in a range of cell types. The dysregulation of PINK1 is associated with the pathogenesis and development of mitochondrial-associated disorders. Many natural products could regulate PINK1 to relieve PINK1-associated diseases. Here, we review the structure and function of PINK1, its relationship to human diseases, and the regulation of natural products to PINK1. We further highlight that the discovery of natural PINK1 regulators represents an attractive strategy for the treatment of PINK1-related diseases, including liver and heart diseases, cancer, and Parkinson's disease. Moreover, investigating PINK1 regulation of natural products can enhance the in-depth comprehension of the mechanism of action of natural products.

Distinct metabonomic signatures of Polygoni Multiflori Radix Praeparata against glucolipid metabolic disorders.

OBJECTIVES: Glucolipid metabolic disorders (GLMD) promote a series of major chronic diseases. Polygoni Multilori Radix Preparata (PMRP) has been widely acknowledged in the prevention and treatment of GLMD. We previously reported that water extract (WE) of PMRP and its major bioactive constituents such as polysaccharides (POL) and 2,3,5,4´-tetrahydroxy-stilbene-2-O-ß-D-glucoside (TSG) could alleviate GLMD. The mitochondrial dysfunction is an important mechanism of GLMD, but the underlying mechanisms behind the regulation of mitochondria to alleviate GLMD by WE, POL from PMRP and TSG are still unknown. METHODS: In this study, we elucidated the effects of WE, POL, and TSG towards regulating the mitochondrial dysfunction and alleviating GLMD using mitochondrial metabonomics. A rat model of GLMD was established by high-sugar and high-fat (HS-HF) diet. Rats were intragastrically given WE, POL, and TSG for 12 weeks. The liver mitochondrial metabolites were analyzed by ultra-high-performance liquid chromatography/mass spectrometry followed by multivariate statistical analysis to identify the differential metabolites and metabolic pathways. KEY FINDINGS: The WE, POL, and TSG could significantly restore the level of endogenous metabolites in liver mitochondria toward normal status. In total, sixteen, seven, and fourteen differential metabolites were identified in the liver mitochondrial samples obtained from the WE, GOL, and TSG groups, respectively. These metabolites were found to be mainly involved in glycerol phospholipid, histidine, alanine, aspartic acid, glutamate metabolism, and arginine biosynthesis. CONCLUSIONS: PMRP could improve the liver mitochondrial function by regulating the mitochondrial metabolic pathways to alleviate GLMD. Therefore, the application of PMRP might be a promising mitochondrial regulator/nutrient for alleviating GLMD-associated diseases and the mitochondrial metabonomics might provide insights into the evaluation of the efficacies and mechanisms of action of drugs.

Remedying the Mitochondria to Cure Human Diseases by Natural Products.

Mitochondria are the 'engine' of cells. Mitochondrial dysfunction is an important mechanism in many human diseases. Many natural products could remedy the mitochondria to alleviate mitochondria-involved diseases. In this review, we summarized the current knowledge of the relationship between the mitochondria and human diseases and the regulation of natural products to the mitochondria. We proposed that the development of mitochondrial regulators/nutrients from natural products to remedy mitochondrial dysfunction represents an attractive strategy for a mitochondria-involved disorder therapy. Moreover, investigating the mitochondrial regulation of natural products can potentiate the in-depth comprehension of the mechanism of action of natural products.

Muscle Fatigue-Alleviating Effects of a Prescription Composed of Polygonati Rhizoma and Notoginseng Radix et Rhizoma.

Long-term muscle fatigue is a major cause of injury. Drugs/nutrients from herbal medicines that prevent fatigue remain a major research focus. In China, a prescription composed of Polygonati Rhizoma and Notoginseng Radix et Rhizoma has been commonly used as a herb and food nutrient, providing protection against fatigue in the clinic. To date, the mechanisms through which this prescription prevented fatigue are unknown. Here, we identified the effects of this prescription on muscle fatigue based on energy and oxidation regulation. Fatigue mouse models were produced through weight-bearing exhaustive swimming. Mice were intragastrically administered prescription extracts (1 and 2 g/kg) for four weeks. Changes in exhaustive swimming times, antifatigue biochemical indicators, oxidative status, and energy metabolism were investigated. The prescription prolonged the exhaustive swimming time of the mice. The content of lactic acid and blood urea nitrogen in the serum was also markedly reduced by the prescription. The content of liver glycogen and lactate dehydrogenase in the serum increased. The prescription also significantly reduced malondialdehyde levels and increased the levels of superoxide dismutase and glutathione peroxidase. The levels of ATPase, complexes I and II in the mitochondria of hind-leg skeletal muscle, and serum creatine kinase also increased in response to the prescription. Our results indicated that the prescription could effectively alleviate muscle fatigue status by promoting energy metabolism and antioxidation ability. The prescription therefore represents a useful drug/nutrient strategy to alleviate muscle fatigue.

[Comparative Study on Protection Effects of CCl4-Induced Acute Liver Injury of Different Prepared Products from Gardenia jasminoides Fruits in Rats].

Objective: To provide the experimental evidence for the appropriate selection of the different prepared products from Gardenia jasminoides fruits by comparing their protection effects on carbon tetrachloride（ CCl4）-induced acute liver injury. Methods: The activities of ALT,AST,ADA,LDH,ALP and contents of PA,TP,TBIL,DBIL,TBA in serum,the activities of SOD and the content of MDA in liver tissue were measured in acute liver injury rats by carbon tetrachloride. Also the pathological changes of liver tissues were examined under microscope. Results: The biochemical indexes of AST,ALT,TBA,ADA,LDH and MDA were significantly improved in all groups of prepared products from Gardenia jasminoides fruits,but not SOD and ALP. The lesions of liver tissue had different degrees of reduction. Conclusion: The different prepared products from Gardenia jasminoides fruits had the effects of liver protection. The nut of Gardeniae Fructus was superior to the peel in enzyme decreasing and liver protection. The crude was superior to the stir-cooked in enzyme decreasing and liver protection.

[Study on the chemical components of Gardenia jasminoides (II)].

OBJECTIVE: To investigate the chemical components of Gardenia jasminoides. METHODS: Various column chromatography were used in the isolation and purification, and physiochemical constant determination and spectral analysis were adopted to idenitify the chemical structures. RESULTS: Ten compounds were isolated and identified as jasminoside A(1), epijasminoside A(2), 6-O-methylscandoside methyl ester (3), 6-O-methyldeacetylasperulosidic acid methyl ester (4), gardenoside (5), phenylmethol (6), 4-hydroxy-phenylmethol-O-beta-D-glucopyranosyl- (1-->6) -beta-D-glucopyranoside (7), 3,4-dihydroxy-phenylmethol-O-beta-D-glucopyranosyl-(1-6)-beta-D-glucopyranoside (8), 3-hydroxy4-methoxy-phenylmethol-O-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranoside (9), 3-hydroxy-4-methoxyphenylmethol-O-beta-D-glucopyranoside (10). CONCLUSION: Compounds 6 -10 are isolated from this plant for the first time.

[Treatment of premature ovarian failure by bushen huoxue recipe combined estrogen and progesterone: a clinical research].

OBJECTIVE: To observe the clinical efficacy of bushen huoxue recipe (BHR) combined estrogen and progesterone in treating premature ovarian failure (POF), and to explore an effective treatment program of POF by integrative medicine. METHODS: Totally 265 POF patients were randomly assigned to 3 groups, i.e., Group I (86 cases, treated by BHR),Group II (88 cases,treated by conjugated estrogens and medroxyprogesterone acetate), and Group III (91 cases,treated by BHR +conjugated estrogens and medroxyprogesterone acetate). The therapeutic course for each group was 6 months. The main symptoms (including menstrual cycle, hectic fever, night sweat, vaginal dryness, and low libido), laboratory indices [including follicle stimulating hormone (FSH), luteotropic hormone (LH), estradiol (E2), and inhibin B (INH-B)], B-ultrasound indicators (including endometrial thickness, ovarian volume, and antral follicle count), and adverse reactions were observed in the three groups at the end of treatment and 6 months after treatment. RESULTS: Compared with before treatment, the main symptoms, laboratory indices, and B-ultrasound indicators were statistically improved in the three groups at the end of treatment and 6 months after treatment (P <0.05, P <0.01). Better effects were obtained in Group III in improving symptoms of the menstrual cycle, vaginal dryness, and low libido, lowering levels of FSH and LH, elevating levels of E2and INH-B, and ameliorating the endometrial thickness, the ovarian volume, and the antral follicle count (P <0.05, P <0.01). No obvious adverse reaction occurred in the three groups. CONCLUSION: BHR combined estrogen and progesterone showed better clinical efficacy than use of BHR or estrogen/progesterone alone, indicating it was an effective treatment program for POF.

[Study on the chemical components of Gardenia jasminoides].

OBJECTIVE: To investigate the chemical components of Gardenia jasminoides. METHODS: Various column chromatography were used in the isolation and purification. Physiochemical constant determination and spectral analysis were adopted to determine the chemical structures. RESULTS: Ten compounds were isolated and elucidated as syringic acid (1), syringaldehyde (2), vanillic acid (3), 3-hydroxy-vanillic acid (4), 3, 4, 5-trimethoxy-phenol (5), 4-hydroxy-3,5-dimethoxy-phenol (6), 4-methoxy-benzaldehyde (7), 7-hydroxy-5-methoxy-chromone (8), crocin-1 (9), crocin-2 (10). CONCLUSION: Compounds 2, 4 - 8 are first isolated from this plant.

[Determination of metal by liquid electrode discharge atomic emission spectrometry with a new design].

A liquid electrode discharge atomic emission spectrometry has been developed with a new design. Plasma fluctuation from the variations in the gap between the W anode and liquid cathode was eliminated by providing a sawtooth-shaped drainage structure. The sawtooth was placed at a distance of 2 mm from the glass capillary top. When a solution is pumped through a glass capillary, the liquid drop forms and rises and on reaching the maximum size collapses while the next drop forms. This results in a continuous change in the interelectrode distance which will cause the discharge current to change, plasma flickers and is extinguished. With the new design, the surface tension of the drop was destroyed before its growing up, and the solution was flowing along the drainage groove. The discharge can last for 3 hours at least with such arrangement. The analytical response curves for lead, chromium, cadmium, zinc, vanadium, nickel, copper, silver and cobalt demonstrated good linearity. The limit of detections of lead, chromium, cadmium, zinc, vanadium nickel, copper, silver and cobalt were determined to be 0.08, 0.61, 0.48, 1.60, 10.88, 0.48, 0.084, 0.048 and 0.27 mg x L(-1) respectively.

[Determination of geniposide and croein-1 in different breed of fructus gardeniae].

OBJECTIVE: To determinate geniposide and croein-1 in Fructus Gardeniae from different breeds. METHODS: RP-HPLC method was adopted. The chromatographic separation was performed on an Eclipse XDB-C18 column (250 mm x 4.6 mm, 5 microm, Agilent). The mobile phase was a mixture of acetonitrile-0.1% phosphoric acid aqueous solution in gradient elution. The wavelength of 238 nm and 440 nm was selected to determinate geniposide and crocins simultaneously. RESULT: The contents of geniposide and croein-1 in different breeds of Fructus Gardeniae are different. CONCLUSION: This method is simple and repeatable, and could be used for the quality control of Fructus Gardeniae.

[Study on effects of acupuncture on mice dysmenorrhea model and the mechanism].

OBJECTIVE: To probe the mechanism of acupuncture in treatment of dysmenorrhea. METHODS: Adult mice with no pregnancy were randomly divided into a normal group, a model group, an acupuncture group and a medication group. The model group, the acupuncture group and the medication group were modeled by Diethylstilbestrol and Ocytocin. For the acupuncture group, at the 7th day of modeling, acupuncture was given at "Sanyinjiao" (SP 6), "Diji" (SP 8), once a day, for 5 days; and at the 7th day of modeling, Yimucao Gao 0.6 mg/g was given intragastrically to the medication group for 5 days. The stretching latent period and the number of stretching within 30 min were observed, and mRNA levels of ocytocin receptor (OctR) and vasopressin receptor (VasR) in the uterus tissue were detected with RT-PCR method. RESULTS: Compared with the model group, the stretching latent period extended (P < 0.05) and the number of stretching within 30 min significantly decreased (P < 0.05); and there were significant differences in the mRNA levels of ocytocin receptor and vasopressin receptor in the uterus tissue in the model group as compared with those in other 3 groups (P < 0.05, P < 0.01). CONCLUSION: Acupuncture can improve the dysmenorrheal symptom to a certain extent, and the mechanism is possibly related to regulative effects of acupuncture on hormones-mediating receptors in mice.

[Effect of acupuncture on Cx43 knock-out mice dysmenorrhea response].

OBJECTIVE: To observe the effect of acupuncture on dysmenorrhea response of Cx43 knock out mice. METHODS: Two-months-old heterozygote [Cx43(+/-)] type and wild type [Cx43(+/+)] female mice (20 mice/type) were allocated into normal group, model group, acupuncture group and Yimucao Gao (Extractum Leonuri Inspissatum) group randomly. Dysmenorrheal model was established by feeding the mouse with diethylstilbestrol (2 mg/g) once daily for 12 days. Ocytocin (i. p. 2 U/kg) was injected on the 12th day 1 h later after the feeding. Acupuncture of "Sanyinjiao" (SP 6) and "Diji" (SP 8) was given to mice of acupuncture group, once daily for 5 days from the 7th day on after modeling. The latency of body-writhing and the writhing number were measured. Ocytocin receptor (Oct-R) mRNA and vasopressin receptor (Vas-R) mRNA expression in the uterus tissue was detected by using reverse transcription polymerase chain reaction (RT-PCR) technique, and Oct-R expression was detected with immunohistochemistry after fixating and sectioning the uterus tissue. RESULTS: In comparison with their individual normal group, the latency of body-writhing of model groups in Cx43 (+/+) and Cx43 (+/-) mice shortened considerably, while the writhing number increased significantly (P<0.01). Compared with the corresponding model group, the writhing latencies of acupuncture and Yimucao Gao groups in Cx43 (+/+) mice and that of Yimucao Gao group in Cx43 (+/-) mice increased remarkably, and the writhing numbers of acupuncture and Yimucao Gao groups in Cx43 (+/+) mice and that of Yimucao Gao group in Cx43 (+/-) mice reduced markedly (P<0.05). In Cx43 (+/+) and Cx43 (+/-) mice, compared with their individual normal group, Oct-R and Vas-R mRNA expressions and Oct-R expression in model group were upregulated obviously (P<0.05). Compared with the corresponding model group, Oct-R and Vas-R mRNA expressions and Oct-R expression of acupuncture and Yimucao Gao groups in Cx43 (+/+) mice, and those of Yimucao Gao group in Cx43 (+/-) mice were down-regulated significantly (P<0.05). No significant differences were found between acupuncture and corresponding model groups in Cx43 (+/-) mice in the above-mentioned indexes (P>0.05). CONCLUSION: Acupuncture can inhibit diethylstilbestrol + ocytocin induced body writhing response in Cx43 (+/+) mice rather than in Cx43 (+/-) mice, which is closely related to its effects in down-regulating Oct-R mRNA, Vas-R mRNA and Oct-R expression.

[Study on fingerprints of Citrus aurantium from different places by capillary electrophoresis].

OBJECTIVE: To develop a high performance capillary electrophoresis method for Citrus aurantium fingerprints to control its quality. METHOD: The background electrolyte (BGE) was an 80 mmol x L(-1) boric acid solution containing 15 mmol x L(-1) borate. The pH of the BGE was adjusted to 9.70 with KOH solution. The detection wavelength was 201 nm and a voltage of 16 kV was applied. The sample hydrodynamic injection was 0.4 ps with a duration time of 8 sec. C. aurantium was extracted by water and a set of capillary electrophoresis fingerprints (CEFP) containing 12 co-possessing peaks was obtained. RESULT: There were good similarities between the standard CEFP and each set of CEFP of C. aurantium collected from eleven different places, and their similarity coefficients were between 0.973 and 0.996. CONCLUSION: The CEFP has acceptable precision, reproducibility and stability and can be used for the quality control of C. aurantium.

[Influence of acupuncture on the immune function of immunosuppressive Cx43 knockout mice].

OBJECTIVE: To observe the influence of acupuncture on the immune function in immunosuppressive Cx43 knockout mice so as to explore the relationship between connexin 43 (Cx43) and acupuncture signal transmission. METHODS: Eighteen male Cx43 knockout mice (Cx43 + / -, 8-9 weeks old) and eighteen wide-type mice (Cx43 + / + ) were divided into normal group, model group and acupuncture group randomly, with 6 cases in each. The immunosuppressive mice model was established by intraperitoneal injection of Cyclophosphamide. Mice in acupuncture group were treated with manual acupuncture of "Zusanli" (ST 36) and "Guanyuan" (CV 4), once daily for 7 days. Spleen index, thymus index, number of leukocytes in the peripheral blood were calculated and the percentage of T lymphocyte subpopulation was detected by using flow cytometry. RESULTS: Compared with normal control group, the spleen index, thymus index and leukocyte number of model group in both Cx43 + / + mice and Cx43 + / - mice were obviously lower (P < 0.05, 0.01), while in Cx43 + / + mice and in comparison with model group, the spleen index, thymus index and leukocyte number of acupuncture group were significantly higher (P < 0.05, 0.01) and no significant differences were found between acupuncture group and control group (P > 0.05). But in Cx43 + / - mice , no obvious differences were found between acupuncture and model groups in the aforementioned 3 indexes (P > 0.05), showing a disappearance of the effect of acupuncture in raising immune function after Cx43 knockout. There were no obvious differences between two control groups and between two model groups in the 3 indexes of Cx43 + / + mice and Cx43 + / - mice. The immune function of Cx43 + / + mice was obviously stronger than that of Cx43 + / - mice in acupuncture group. CONCLUSION: Knockout of Cx43 gene inhibits the effect of acupuncture in reinforcing mouse immunity, suggesting an important role of Cx43 in the transmission of acupuncture signals for adjusting immunity function.

[A survey of neurological medical care resources in grade II suburban and urban hospitals in Beijing].

OBJECTIVE: To survey the current availability of expertise in diagnosis and treatment of neurological diseases in grade II hospitals (primary hospitals) in Beijing. METHODS: Observation, personal in-depth interview and structured questionnaire methods were conducted to survey the status of neurology health care system. RESULTS: From June to August 2005, 66 grade II suburban and urban hospitals in Beijing of China were investigated. There were 66 grade II hospitals in Beijing (suburban 34; urban 32). Cerebrovascular disease was the most common disease. Accounting for 84% of the hospitalized cases in inpatients neurology departments. In urban areas, the proportion of grade II and grade III hospitals (referral hospitals) was 58:60, but in suburban and rural areas, the proportion was 48:6. In suburban and rural areas. Only 64.7% of the hospitals could provide urokinase treatment, 26.5% could provide recombinant tissue plasminogen activator (rt-PA) treatment and 58.8% had standardized operation protocol. CONCLUSIONS: The grade II hospitals in suburban areas have heavy grave responsibility to deal with cerebrovascular disease, but these hospitals are in lack of specialists, diagnostic equipment and stroke treatment protocols and could not satisfy the medical demand. It is suggested that in the grade II hospitals in suburban areas of Beijing, strengthening personnel training, establishing primary stroke center and setting up telestroke emergency care systems are urgently needed.

[Optimization of the extraction technology for the essential oil from Mosla chinensis Maxim].

OBJECTIVE: To make sure the best extraction technology of essential oil from Mosla chinensis Maxim. METHODS: By single-factor experiment, quantity of water, degree of crush, time of extraction and soakage and the part of medicinal materials were studied. RESULTS: The best extractin technology of Mosla chinensis Maxim was established.