Mechanisms for the biological activity of Gastrodia elata Blume and its constituents: A comprehensive review on sedative-hypnotic, and antidepressant properties.

BACKGROUND: Insomnia and depressive disorder are two common symptoms with a reciprocal causal relationship in clinical practice, which are usually manifested in comorbid form. Several medications have been widely used in the treatment of insomnia and depression, but most of these drugs show non-negligible side effects. Currently, many treatments are indicated for insomnia and depressive symptom, including Chinese herbal medicine such as Gastrodia elata Blume (G. elata), which has excellent sedative-hypnotic and antidepressant effects in clinical and animal studies. PURPOSE: To summarize the mechanisms of insomnia and depression and the structure-activity mechanism for G. elata to alleviate these symptoms, particularly by hypothalamic-pituitary-adrenal (HPA) axis and intestinal flora, aiming to discover new approaches for the treatment of insomnia and depression. METHODS: The following electronic databases were searched from the beginning to November 2023: PubMed, Web of Science, Google Scholar, Wanfang Database, and CNKI. The following keywords of G. elata were used truncated with other relevant topic terms, such as depression, insomnia, antidepressant, sedative-hypnotic, neuroprotection, application, safety, and toxicity. RESULTS: Natural compounds derived from G. elata could alleviate insomnia and depressive disorder, which is involved in monoamine neurotransmitters, inflammatory response, oxidative stress, and gut microbes, etc. Several clinical trials showed that G. elata-derived natural compounds that treat depression and insomnia have significant and safe therapeutic effects, but further well-designed clinical and toxicological studies are needed. CONCLUSION: G. elata exerts a critical role in treating depression and insomnia due to its multi-targeting properties and fewer side effects. However, more clinical and toxicological studies should be performed to further explore the sedative-hypnotic and antidepressant mechanisms of G. elata and provide more evidence and recommendations for its clinical application. Our review provides an overview of G. elata treating insomnia with depression for future research direction.

Triterpenoid acids from medicinal mushroom Inonotus obliquus (Chaga) alleviate hyperuricemia and inflammation in hyperuricemic mice: Possible inhibitory effects on xanthine oxidase activity.

The purpose of this study was to explore the hypouricemic effect in hyperuricemia mice of triterpenoid acids from Inonotus obliquus (TAIO), and decipher of the underlying xanthine oxidase inhibitory mechanism. Measurement of xanthine oxidase (XO) inhibitory activity was assayed. Organ indexes and serum biochemical indicators were measured in potassium oxonate-induced hyperuricemia mice. Studies showed that TAIO had the strong inhibitory effect on XO activity, and its inhibition type was mixed and reversible. In vivo, TAIO decreased efficiently uric acid level, hepatic XO, serum blood urea nitrogen activities in hyperuricemia mice. Indicating that TAIO may ameliorate kidney damage and relieve inflammation in hyperuricemic mice, and had the inhibitory effect on XO activity. Furthermore, eight triterpenoids were identified by Ultra performance liquid chromatography electrospray quadrupole time of flight mass spectrometry. These findings proved that triterpenoids from Inonotus obliquus would have potential biological characteristics and effect on controlling hyperuricemia and gout as an active supplement. PRACTICAL APPLICATIONS: There are a large amount of evidence indicating that hyperuricemia and gout are related to the hypertension and obesity. And gout and hyperuricemia are also possible connection with cardiovascular disease and metabolic syndrome. Currently, xanthine oxidase is the target of many kinds of chemical drugs at present, but the therapeutic drugs used in clinical medicine will produce more or less side effects. Therefore, the aim of this study was to explore the material basis of effective substances for reducing uric acid in Inonotus obliquus and to evaluate its effect. This study can provide a promising application of Inonotus obliquus in the fields of functional foods or medicines for gout and hyperuricemia.

Enzymolysis peptides from Mauremys mutica plastron improve the disorder of neurotransmitter system and facilitate sleep-promoting in the PCPA-induced insomnia mice.

ETHNOPHARMACOLOGY RELEVANCY: For many centuries, Mauremys mutica is highly valued as a food homologous Chinese herbal medicine. It has been considered useful to sedate, nourish brain and promote sleep. However, the animal experimental evidence of its sleep-promoting activity is missing in literature. AIM OF THE STUDY: In this study, PCPA-induced insomnia model was used to explore the sleep-promoting mechanism of enzymolysis peptides from PMM, and its main composition and chemical structure were analyzed. MATERIALS AND METHODS: Experiments were performed using PCPA-induced insomnia model, all animals were intraperitoneally injected with PCPA (350 mg/kg·d) for two days. The sleep-promoting effect evaluated using measuring content of 5-HT, GABA, DA, IL-1, BDNF and expression of 5-HT1A receptor and GABAA receptor α1-subunit in mice brain. Primary structure of peptides was identified by HPLC-ESI-QqTOF-MS/MS. RESULTS: Compared with the model group, the content of 5-HT, GABA, IL-1, BDNF in mice brain of PMM peptide groups was increased to varying degrees, the content of DA was decreased, and the gene transcription and protein expression of 5-HT1A receptor and GABAA receptor α1-subunit were almost all returned to normal levels. In addition, the primary structures of most abundant nine typical peptides in PMM peptides were identified. CONCLUSIONS: The results showed that PMM peptides could improve the disorder of neurotransmitter system, restore compensatory over-expression 5-HT1A receptor and GABAA receptor α1-subunit, and have a good sleep-promoting effect. The specific amino acid composition, sequence and glycosylation modification of PMM peptides may be the key reason for their activity, which lays a foundation for the subsequent development of sleep-promoting peptide products.

Comparisons of carbohydrate-utilizing enzymes inhibitory effects and chemical profiles of five deeply colored food extracts.

Deeply colored food has attracted great interest of researchers as they can be loaded with health-promoting compound. Extracts from five deeply colored food (Black currant, Wild rice 1, Black bean hull, Wild rice 2, and Mulberry) were chosen and carried to evaluate the carbohydrate-utilizing enzymes inhibitory effects and compare the chemical compound profiles to lock the candidate compound for the enzymes. Although the contents of total phenolics in five extracts were at comparable levels, the anthocyanins and flavonoids contents varied widely. Especially for the extracts from Black bean hull, the compositions of phenolics and anthocyanins characterized by UPLC-QTOF-MS/MS were significantly different from other samples. In addition, the inhibitory effects of Black bean hull on α-amylase demonstrated approximately half of that of acarbose at the same concentration while its inhibitory effect on α-glucosidase was doubled of that of acarbose. The inhibition kinetics illustrated that Black bean hull had reversible and uncompetitive inhibitory effect on α-glucosidase with the IC50 value being 11.37 µg/ml. Pearson's correlation analysis showed that the contents of total flavonoids and α-glucosidase inhibition were more relevant, and the B-type proanthocyanins was presumably the main active substance. PRACTICAL APPLICATIONS: Carbohydrate-utilizing enzymes are potential therapeutic targets of diabetes since they could balance the postprandial blood glucose. Anthocyanins, the natural pigments with flavonoid structures, are being attracted by citizens and researchers because of their high antioxidant effect. Anthocyanin extracts from Black bean hull among other four deeply colored food could be an alternative anti-hyperglycemic agent and copigments in anthocyanin extracts are the candidate for α-glucosidase inhibition.

Intervention on immunodeficiency mice and structural identification of enzymatic peptides from Mauremys mutica and Cuora trifasciata.

ETHNOPHARMACOLOGY RELEVANCY: Mauremys mutica (Asian yellow pond turtle, YPT) and Cuora trifasciata (Chinese three-striped box turtle, TBT) are traditional Chinese medicine. They possess many biological characteristics, such as immune-enhancement, anti-inflammatory, anti-cancer effects. They have been used as folk anti-cancer drugs in central and southern China for a long time. However, there was no reports of comparing the immune-enhancement effect of YPT and TBT, nor of identifying the structures of YPT peptides and TBT peptides. AIMS OF THE STUDY: The aim of this study was to evaluate the protective efficacy of YPT and TBT on immunodeficient mice and to compare the primary structures of YPT peptides and TBT peptides. MATERIALS AND METHODS: The protein extracts were extracted using 100 °C water, and peptides were obtained by hydrolyzing protein extracts using alkaline protease. Cyclophosphamide (CTX) was used to induce immunodeficiency in mice. The immune enhancement effect was evaluated by measuring body weight gain curve, thymus index, spleen index, serum SOD activity and GSH-Px activity. Primary structure of peptides was identified by HPLC-ESI-MS/MS. RESULTS: The protein extracts and peptides of the YPT and TBT had certain recovery effects on immunodeficient mice. YPT peptide has the best effect on the recovery of damaged immune organs and the improvement of SOD and GSH-Px activities in mice. In the identification of the primary structure of the polypeptide, we find that YPT and TBT contain some similar peptides as well as different peptides, and the concentration of the peptide segments in HPLC data is very different. The difference of biological activity may be determined by both the difference of specific peptide structure and concentration. CONCLUSIONS: Two kinds of healthy turtle protein extracts and peptides could have immune-enhancement function, and peptides obtained by enzymatic hydrolysis of YPT protein extracts have the best immune-enhancement effect. The identification of the primary structure of the peptide segment preliminarily showed that its biological activity was affected by the amino acid sequence and the concentration of part of the peptide segment. It laid a foundation for the follow-up search of immune-enhancement peptides and the development of high-value YPT products.

Effect of ultrasonic and ball-milling treatment on cell wall, nutrients, and antioxidant capacity of rose (Rosa rugosa) bee pollen, and identification of bioactive components.

BACKGROUND: Bee pollen has been regarded as a complete nutritional human dietary supplement but its nutrient absorption and biological effects may be restricted by the complex pollen wall. The aim of this study was to explore the effects of ultrasonic and ball-milling treatment on the release of nutritional components and on in vitro and in vivo antioxidant effects of rose (Rosa rugosa) bee pollen. RESULTS: Bee pollen walls were broken to varying degrees, nutrients were released, and in vitro and in vivo antioxidant effects of bee pollen were improved. The scavenging effects of 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2'-azinobis(3-ethylbenzothiazolone-6-sulfonic acid) (ABTS) radicals, and oxygen radical absorbance capacity (ORAC) were improved. In aging mice, wall-breaking treatment led to better organ recovery, enhanced superoxide dismutase (SOD) and catalase (CAT) effects, and malondialdehyde (MDA) reduction. Eight compounds of rose bee pollen ethanol extract, including isorhamnetin 3-O-diglucoside and N', N″, N‴-dicaffeoyl p-coumaroyl spermidine were identified by ultra-performance liquid chromatography electrospray ionization quadrupole time of flight mass spectrometry (UPLC-ESI-QTOF-MS/MS) assay. CONCLUSION: This study showed that ultrasonic treatment had greater wall-disruption effects of bee pollen on nutrient release and antioxidant effect promotion. In conclusion, rose bee pollen, with wall-breaking treatments, may have potential value as an ingredient in functional food processing. © 2019 Society of Chemical Industry.

Highly Acylated Anthocyanins from Purple Sweet Potato ( Ipomoea batatas L.) Alleviate Hyperuricemia and Kidney Inflammation in Hyperuricemic Mice: Possible Attenuation Effects on Allopurinol.

Allopurinol is the first-line medication for hyperuricemia treatment. However, severe drug-related adverse effects have often been reported among patients who received allopurinol administration. This study is aimed at evaluating the possible attenuation effects of highly acylated anthocyanins from purple sweet potato (HAA-PSP) on hyperuricemia and kidney inflammation in hyperuricemic mice treated with allopurinol. In comparison with 5 mg kg-1 allopurinol used alone, the combination of 25 mg kg-1 HAA-PSP and 2.5 mg kg-1 allopurinol could not only reduce serum uric acid level in hyperuricemic mice but also attenuate the kidney damage, as indicated by the level of serum biomarkers as well as histopathological examination. The inflammatory response was partially mitigated by inhibiting the protein expression of typical cytokines in the kidney. Our findings provide new evidence for the supplementary therapeutic potential of HAA-PSP with allopurinol on hyperuricemia and inflammation-related syndromes. Moreover, this study provides a theoretical basis for assessing the potential of anthocyanin-rich foods in health.

Comparison and screening of bioactive phenolic compounds in different blueberry cultivars: Evaluation of anti-oxidation and α-glucosidase inhibition effect.

This study was aimed to investigate antioxidation and α-glucosidase inhibition of the bioactive compounds in three cultivars of blueberry ('Northland' (NL) from the hybrid blueberry (V. corymbosum L.×V. angustifolium Aiton), 'Britewell' (BW), and 'Gardenblue' (GB) from the rabbiteye blueberry (Vaccinium ashei Reade)). A total of eighteen anthocyanins were identified and quantified in Anthocyanins (ACNs), among which four acylated anthocyanins were exclusively found in Northland. The blueberry anthocyanin extracts (BAEs) were further measured the antioxidant activity and α-glucosidase inhibition effect. Northland BAEs exhibited significantly superior antioxidant activity compared with BAEs of other cultivars, and the antioxidant activity was correlated with the content of anthocyanins. However, α-glucosidase inhibition test showed that Britewell BAEs had the strongest inhibitory effect. BAEs were further separated into anthocyanin fraction (AF) and copigment fraction (CF). Fifteen phenolic acids and four iridoids were identified in CF. In terms of α-glucosidase inhibition effects, the CF from three cultivars could inhibit α-glucosidase in a dose-dependent manner, while the AF did not show significant inhibitory effects. The blueberry exhibits excellent antioxidant activity and α-glucosidase inhibition.

Characterization and hepatoprotective activity of anthocyanins from purple sweet potato (Ipomoea batatas L. cultivar Eshu No. 8).

The hepatoprotective activity of anthocyanin-rich purple sweet potato extract (APSPE) was demonstrated. Sixty mice were randomly divided into six groups: control group [without carbon tetrachloride (CCl4) or APSPE]; model group (with CCl4 only); positive control group (50 mg/kg body weight silymarin); low-dose group (100 mg/kg body weight APSPE); medium-dose group (200 mg/kg body weight APSPE); and high-dose group (400 mg/kg body weight APSPE). After 10 days intragastric administration of the respective supplements, the mice in all groups except control were injected intraperitoneally with CCl4 (0.15% in arachis oil, 10 mL/kg body weight, intravenous). Twelve hours after CCl4 injection, the mice were measured in terms of liver index, levels of aspartate aminotransferase and alanine aminotransferase in serum, as well as glutathione, superoxide dismutase, and malondialdehyde in liver homogenate. Additionally, the livers of mice were stained with hematoxylin and eosin and sectioned for observation. Nineteen purple sweet potato anthocyanins were identified from the purple sweet potato cultivar Eshu No. 8 and analyzed by liquid chromatography- electrospray ionization-tandem mass spectrometry. Peonidin 3-coumaryl-p-hydroxybenzoyl sophoroside-5-glucoside was first identified in purple sweet potato. The results showed that anthocyanins in Eshu No. 8 had good hepatoprotective activity.

Inhibitory effect of Gardenblue blueberry (Vaccinium ashei Reade) anthocyanin extracts on lipopolysaccharide-stimulated inflammatory response in RAW 264.7 cells.

Blueberries are a rich source of anthocyanins, which are associated with health benefits contributing to a reduced risk for many diseases. The present study identified the functional Gardenblue blueberry (Vaccinium ashei Reade) anthocyanin extracts (GBBAEs) and evaluated their capacity and underlying mechanisms in protecting murine RAW 264.7 cells from lipopolysaccharide (LPS)-stimulated inflammation in vitro. Enzyme-linked immunosorbent assay (ELISA) kit results showed that GBBAEs significantly inhibited the production of nitric oxide (NO), prostaglandin E2 (PGE2), interleukin-6 (IL-6), IL-1ß, and interferon-γ (INF-γ). Real-time polymerase chain reaction (PCR) analysis indicated that the mRNA expression levels of IL-6, IL-1ß, tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1 (MCP-1), and cyclooxygenase 2 (COX-2) were suppressed in LPS-stimulated RAW 264.7 cells. Additionally, Western blot analysis was used to evaluate the relative protein expression levels of COX-2 and nuclear factor-κB p65 (NF-κBp65). All these results suggested the potential use of GBBAEs as a functional food for the treatment of inflammatory diseases.

Effects of anthocyanins from purple sweet potato (Ipomoea batatas L. cultivar Eshu No. 8) on the serum uric acid level and xanthine oxidase activity in hyperuricemic mice.

This study was aimed at evaluating the hypouricemic effect of the anthocyanin-rich purple sweet potato extract (APSPE). In vitro, APSPE has been proved to significantly inhibit XO activity in a dose-dependent manner. In vivo, APSPE could not only inhibit the XO activity in mouse liver, but also reduce the serum uric acid level in hyperuricemic mice and affect the expression of mRNA levels of related renal transporters, such as mURAT1, mGLUT9, mOAT1 and mOCTN2. Moreover, APSPE could effectively regulate BUN and Cr levels to normal and decrease the inflammatory cellular influx in the tubule of the hyperuricemic mice. This study indicates the potential clinical utility of APSPE as a safe and effective anti-hyperuricemia bioactive agent or functional food.

Anti-diabetic effects of polysaccharides from Talinum triangulare in streptozotocin (STZ)-induced type 2 diabetic male mice.

The present study evaluated the anti-diabetic effects of the polysaccharides obtained from Talinum triangulare (TTP). Two TTP doses (150 mg/kg and 300 mg/kg · bw/d) were administered orally to normal and streptozotocin (STZ)-induced type 2 diabetic male Kunming mice, respectively. The TTP hypoglycemic and hypolipidemic effects were evaluated by testing the fast blood glucose (FBG) level, fasting serum insulin (FINS), and serum lipids (TC, TG, HDL, LDL) as well as the body, hepar and kidney weights. After four weeks administration, the low-dose group 150 mg/kg · bw/d) and high-dose group (300 mg/kg · bw/d) showed a marked FBG fall rate of 29.85% and 41.18% (FBG fall rate% = ((Diabetic control--TTP group)/Diabetic control) × 100%). The results of FBG and serum lipids indicate that TTP possess significant hypoglycemic effect, but no significant hypolipidemic effect. These results suggest the potential use of TTP as a functional food for the treatment of type 2 diabetic mellitus (T2DM).

Antitumor efficacy in H22 tumor bearing mice and immunoregulatory activity on RAW 264.7 macrophages of polysaccharides from Talinum triangulare.

The aim of this paper was to study the antitumor and immunoregulatory activities of a polysaccharide (TTP) from Talinum triangulare. The molecular weight of TTP-IV was 49.9 kDa. The monosaccharide composition analysis of TTP-IV revealed that it was a heteropolysaccharide consisting of rhamnose, arabinose, mannose and galactose with a molar ratio of 1.22 : 1.00 : 1.05 : 1.51. The results of the in vivo study showed that TTP (200 mg per kg bw) significantly inhibited the growth of tumor by 49.07% in H22-bearing Kunming mice. In vitro, the growth of primary murine macrophages was promoted by TTP in a dose- and time-dependent manner significantly. Besides, RAW 264.7 cells were activated by TTP to produce NO and the toxicity of RAW 264.7 supernatant was markedly enhanced in vitro. The levels of iNOS, TLR2, TLR4 and IL-1ß were obviously increased by TTP. Therefore, it is suggested that TTP can be utilized as a potent antitumor and immunoenhancing material in functional food.

Corn peptides protect against thioacetamide-induced hepatic fibrosis in rats.

Certain bioactive peptides are reported to be able to alleviate hepatic fibrosis. Our previous work has confirmed the hepatoprotective effect of corn peptides (CPs) that are prepared from a high protein by-product, corn gluten meal, on acute liver injury in an animal model. However, the antifibrotic activity of CPs remained to be elucidated. In this study, the hepatoprotective effect of CPs on thioacetamide (TAA)-induced liver fibrosis was tested. Results showed that CPs (100 mg/kg body weight) significantly decreased the levels of alanine transaminase/aspartate transaminase, laminin, type IV collagen, and type III collagen in serum and increased the serum albumin levels and total antioxidant capacity. Additionally, with CP treatment (100 mg/kg body weight), a significant decrease was observed in the levels of malondialdehyde, nitric oxide, hydroxyproline, transforming growth factor ß1, and lactate dehydrogenase activity as well as the liver index, while the activity of superoxidedismutase was significantly increased in livers. The histological and morphological analysis showed that the hepatocyte structure in CP-treated rats was superior to that of TAA-injured rats, and inflammation and fibrosis were also ameliorated. Therefore, CPs can be used as an option for prevention and adjuvant therapy of liver fibrosis.

The Effects of Velvet Antler of Deer on Cardiac Functions of Rats with Heart Failure following Myocardial Infarction.

Velvet antler of deer (VAD) is a commonly-used kidney-Yang supplementing traditional Chinese medication. According to the heart-kidney-related theory, heart Yang originates in kidney Yang and heart failure due to heart Yang deficiency can be treated by tonifying kidney Yang. In this study, we investigated therapeutic effects of VAD on cardiac functions in rats with heart failure following myocardial infarction. Forty-eight male Wistar rats were subjected either to left coronary artery ligation (N = 36) or to sham operation (N = 12). One week after the surgery, rats with heart failure received daily treatment of double-distilled water, captopril or VAD by gavage for consecutively four weeks, while sham-operated animals were given double-distilled water. Ultrasonic echocardiography was adopted to examine cardiac structural and functional parameters and serum brain natriuretic peptide (BNP) concentration was measured using radioimmunoassay. We found that VAD partially reversed changes in cardiac functional parameters and serum BNP levels in rats with heart failure. These results provide further evidence for the heart-kidney-related theory and suggest that VAD might be a potentially alternative and complementary medicine for the treatment of heart failure.

[Analyzing the Chinese medicine pathogenesis of stroke].

Both ischemic and hemorrhage stroke pertain to the category of wind stroke in Chinese medicine (CM). Up to date, it is deemed that the etiology and pathogenesis of wind stroke are wind, fire, sputum, qi, stasis, and deficiency. Among them, it is regarded that wind and fire are the key factors triggering wind stroke. By analyzing the time order and causality, it is found that wind stroke is prior to the onset of wind and fire, wind and fire are the secondary outcomes of wind stroke. By parallel comparing stroke with thromboembolism and hemorrhagic diseases in other Zang-organs, it can be comprehended that the reason why wind symptoms appear in stroke is due to its physiological feature of brain itself. Based on Neijing, the pathogenesis of wind stroke is proposed as follows. Tunnels of viscera (vessels) get lesions. The old pathogenic factors of sputum and stasis or the stasis formed by bleeding inside viscera consume qi, and blood of viscera and damage the spirits hidden in them. The damage of Gan-spirit causes symptoms of stroke, such as hemiplegia, deviation of eyes and mouth, and so on. Wind and fire symptoms are caused by the injury of Gan blood and yin, and/or the stagnation of fire in pericardium (the pathway organ) due to obstruction by old pathogenic factors and stasis (formed by bleeding).

Addictive evaluation of cholic acid-verticinone ester, a potential cough therapeutic agent with agonist action of opioid receptor.

AIM: The purpose of this work was to search for potential drugs with potent antitussive and expectorant activities as well as a low toxicity, but without addictive properties. Cholic acid-verticinone ester (CA-Ver) was synthesized based on the clearly elucidated antitussive and expectorant activities of verticinone in bulbs of Fritillaria and different bile acids in Snake Bile. In our previous study, CA-Ver showed a much more potent activity than codeine phosphate. This study was carried out to investigate the central antitussive mechanism and the addictive evaluation of CA-Ver. METHODS: Testing on a capsaicin-induced cough model of mice pretreated with naloxone, a non-selective opioid receptor antagonist, was performed for the observation of CA-Ver's central antitussive mechanism. We then took naloxone-induced withdrawal tests of mice for the judgment of CA-Ver's addiction. Lastly, we determined the opioid dependence of CA-Ver in the guinea pig ileum. RESULTS: The test on the capsaicin-induced cough model showed that naloxone could block the antitussive effect of CA-Ver, suggesting the antitussive mechanism of CA-Ver was related to the central opioid receptors. The naloxone-urged withdrawal tests of the mice showed that CA-Ver was not addictive, and the test of the opioid dependence in the guinea pig ileum showed that CA-Ver had no withdrawal response. CONCLUSION: These findings suggested that CA-Ver deserved attention for its potent antitussive effects related to the central opioid receptors, but without addiction, and had a good development perspective.

Structural analysis and antitussive evaluation of five novel esters of verticinone and bile acids.

Shedan-Chuanbei powder, a complex of traditional Chinese medicine preparation, which consists of Snake Bile (Chinese name "Shedan") and Fritillariae Cirrhosae (Chinese name "Chuanbei"), is the most popular antitussive and expectorant formulation in Chinese communities. However, the clinical application of Shedan-Chuanbei powder is now stringently limited because of the shortage of the two crude medicinal materials, especially for the sake of animal protection. In addition, the inherent defects of the most of the complex of traditional Chinese medicine such as the indistinct basal pharmacodynamic materials and the difficulties in quality control had blocked them heading into the international medicinal market. So we attempted to seek new substitute for Shedan-Chuanbei powder for antitussive drugs. In order to gain some new compounds with better bioactivity and attenuated toxicity, we tried to combine two kinds of drugs through ester bond. Enlightened with "combination principle" in drug discovery, we synthesized five novel esters of verticinone and bile acids, both of which are the major bioactive components in Shedan-Chuanbei powder. We then evaluated the antitussive activity and the acute toxicity of the five ester-linked compounds. The five ester-linked compounds had much more potent antitussive activity and expectorant activity than single bile acids at the same doses, and had equivalent antitussive activity and expectorant activity in comparison with about double moles dose of the monomer verticinone. Especially, cholic acid-verticinone ester had much more potent antitussive effects than the monomer verticinone or cholic acid at the same dose. A further acute toxicity study showed that the LD(50) values of the five ester-linked compounds exceeded 3.5g/kg by intraperitoneal injection in mice. Based on the studies of pharmacology and acute toxicity, the five ester-linked compounds have synergic pharmacodynamic action and attenuated toxicity compared with single verticinone and single bile acids.

[Experimental study on effect of jiangya maijing liquid on spontaneous hypertension rats fed with high lipid diet].

OBJECTIVE: To observe and identify the effect of Jiangya Maijing Liquid (JYMJL) on spontaneous hypertension rats (SHR) fed with high lipid diet in antagonizing hypertension and hyperlipidemia and improving pathological changes of kidney. METHODS: Forty-two SHR were divided into 5 groups, except Group A, the Groups B-E were fed with high lipid diet, and Group C, D and E was treated with JYMJL, western drug and Niuhuang Jiangya pill respectively. Besides, Group F was set up for control with normal rats fed by normal diet. The changes of blood pressure (BP), biological indices and renal pathology were observed in the 14 weeks' period of observation. RESULTS: (1) BP raised significantly in Group A and B, it became stable in Group C from the 5th week on and was lower than the BP in other groups (P < 0.01). BP in Group F was not changed; (2) The highest level of nitric oxide (NO) was shown in Group F, and that in Group B and E was lower than that in Group C and D; (3) Level of cholesterol was lower in Group A and F than that in Group C, D and E (P < 0.01), and that in Group C was lower than that in Group B and E (P < 0.01 and P < 0.05 respectively); (4) Pathologic examination on kidney showed that no change was found in Group F, the most severe change was shown in Group B among Group B-E, and the improvement after treatment in Group C was better than that in group B (P < 0.01). CONCLUSION: (1) Condition of disease in rats with hypertension complicated with hyperlipidemia was more severe than that with simple hypertension; (2) JYMJL could restrain the developing of hypertension in SHR, the mechanism may be related with the raising of NO; (3) JYMJL has effect of lowering blood lipid; (4) JYMJL has kidney protective effect, it could alleviate the pathological changes in kidney by way of lowering BP and blood lipid.

[Effect of garlicin on adhesion molecules expression and deformability of peripheral neutrophils in patients with acute cerebral infarction].

OBJECTIVE: To observe the effect of garlicin on adhension molecules CD11a and deformability of peripheral neutrophil in patients with acute cerebral infarction (ACI). METHODS: Neutrophils were separated from peripheral blood of healthy subjects and ACI patients, and incubated in 37 degrees C in vitro. The CD11a expression was detected by antibody fluorescence labeling method and the time of neutrophils passing millipore membrane were measured for calculation of the filter index. RESULTS: CD11a expression rate in healthy subjects was 34.64 +/- 25.34%, while in patients was 55.35 +/- 30.54%, difference between them was significant (P < 0.05). After garlicin treatment, it lowered to 49.16 +/- 31.68%, as compared with untreated group, P < 0.05. The neutrophil filter index in healthy group, untreated group, garlicin treated group and Nimodipine treated group was 0.87 +/- 0.46, 6.42 +/- 6.40, 3.47 +/- 3.67 and 5.03 +/- 3.72 respectively, comparison between that in the garlicin treated group and in untreated group showed significant difference (P < 0.05). CONCLUSION: Garlicin could effectively inhibit the CD11a expression in peripheral blood neutrophils and improve the deformability of the neutrophils in ACI patients.