The different effects of psyllium husk and orlistat on weight control, the amelioration of hypercholesterolemia and non-alcohol fatty liver disease in obese mice induced by a high-fat diet.

Obesity is a widespread medical problem, for which many drugs have been developed, each with its own limitations. Orlistat, a lipase inhibitor, functions as a fat absorption blocker and is a widely used over-the-counter drug in China. Psyllium husk, in contrast, is a food source rich in dietary fibre and is beneficial for weight loss because it reduces appetite. Here, it was investigated how psyllium husk treatments affect mice with a high-fat diet (HFD)-induced obesity, using obesity-related indices, metabolism indices, and gut microbiota, compared to orlistat treatments. Orlistat had a greater effect on weight loss, whereas psyllium husk had a greater effect at reducing serum and liver cholesterol and triglyceride levels. Treatments had similar effects on controlling the body fat rate, the expression level of farnesoid X receptor, sterol 27-hydroxylase and oxysterol 7-hydroxylase (CYP7B1) in the liver, and the regulation of major bile acids such as cholic acid, chenodeoxycholic acid, deoxycholic acid, and lithocholic acid in faecal content. However, the expression of CYP7A1 in the liver and the structures of faecal bile acids were different between the two drugs. Furthermore, although they also had similar effects on the gut microbiota at the phylum level, there were differences at the genus level for Roseburia, Bacteroides, Faecalibacterium, Coprobacillus, and Akkernansia, which led to the difference in the serum lipopolysaccharide (LPS) level. Orlistat increased the food intake of the obese mice that were fed a HFD, which led to an increase in water intake, serum triglyceride levels, and lower glucose tolerance. Although orlistat is considered a suitable drug for weight loss, psyllium husk is a comparatively more cost-effective choice for ameliorating hypercholesterolemia and non-alcoholic fatty liver disease caused by a HFD.

The different effects of Chinese Herb Solid Drink and lactulose on gut microbiota in rats with slow transit constipation induced by compound diphenoxylate.

Slow transit constipation (STC) has become an epidemic medical problem. There are several kinds of drugs for constipation; however, each drug has its limitations. The gut microbiota has a close relationship with STC. Lactulose is an effective drug for constipation because it is a kind of bulking laxative and microbioecologic, and it relieves the syndromes of STC. We found that the Chinese Herb Solid Drink (CHSD), which contains medicine food homologous materials such as psyllium husk, sweetalmond, semen sesami nigrum, and hemp seed, has a similar effect on relieving constipation as lactulose, although it has different effects on the gut microbiota. We investigated the mechanisms of CHSD in rats with STC, induced by diphenoxylate, via constipation index and enzyme linked immunosorbent assay (ELISA) analyses using serum and 16S rDNA amplicon and gas chromatography-mass spectroscopy (GC-MS). CHSD enhanced the relative abundance of some types of gut microbiota, such as Blautia, Ruminococcus, Roseburia, Coprococcus, Lachnospira, and Phascolarctobacterium, while lactulose enhanced the relative abundance of Blautia, Phascolarctobacterium, Eubacterium, and Akkernansia in diphenoxylate-induced STC rats. Both CHSD and lactulose enhanced the level of short-chain fatty acids in the faeces of rats; however, the composition of those were different between the two drugs. From the perspective of the gut neuroendocrine system, both CHSD and lactulose could elevate neurotransmitters, such as motilin (MTL) and substance P (SP), which promote intestinal peristalsis and reduce the expression of vasoactive intestinal peptide, which inhibits intestinal peristalsis in the serum of STC rats. CHSD could elevate gastrin expression, which also promoted intestinal peristalsis in serum, while lactulose did not have this effect. Our findings suggest that CHSD may be an effective and safe therapeutic choice for STC.

Cajanolactone A, a stilbenoid from cajanus cajan, prevents ovariectomy-induced obesity and liver steatosis in mice fed a regular diet.

BACKGROUND: Visceral obesity and fatty liver are prevalent in postmenopausal women. The stilbene-rich extract of Cajanus cajan (L.) Millsp. has been reported to prevent ovariectomy-induced and diet-induced weight gain in animal models, and stilbenoids from C. cajan are thought to have the potential to prevent postmenopausal obesity and fatty liver. PURPOSE: Cajanolactone A (CLA) is the main stilbenoid from C. cajan with osteoblastogenic promoting activity. This study investigated the potential of CLA to prevent postmenopausal obesity and fatty liver. Underlying mechanisms were also investigated. METHOD: Ovariectomized C57BL/6 mice fed a regular diet were used as mimics of postmenopausal women and given 10, 20, or 40 mg/kg/d of CLA, 0.1 mg/kg/d of estradiol valerate (EV, positive control), or vehicle (OVX) orally for 16 weeks. Mice of the same age subjected to a sham operation were used as control (Sham). Body weights were recorded every 2 weeks for 16 weeks. Body compositions were analyzed via micro-CT. Serum levels of lipids, adipocytokines and aminotransferases were measured using the relevant kits. mRNA levels of genes of interest were detected by RT-qPCR. Proteomic study of perigonadal white adipose tissue (pWAT) was performed using tandem-mass-tags-based proteomic technology combined with Parallel-Reaction-Monitoring (PRM) validation. RESULTS: CLA showed potential equivalent to that of EV to prevent ovariectomy-induced overweight, obesity, dyslipidemia, liver steatosis and liver dysfunction, but did not prevent uterine atrophy. In the liver, CLA significantly inhibited ovariectomy-induced upregulation in expression of lipogenic genes SREBP-1c and ChREBP, and stimulated the mRNA expression of apolipoprotein B gene ApoB. In pWAT, CLA reversed, or partially reversed ovariectomy-induced downregulation in the expression of a number of metabolism- and mitochondrial-function-related proteins, including Ndufa3, Pcx, Pdhb, Acly, Acaca, Aldh2, Aacs and Echs1. In addition, ovariectomy-inhibited mRNA expression of Pdhb, Aacs, Acsm5, Echs1, and Aldh2 genes in pWAT was also reversed. CONCLUSION: CLA was demonstrated to be a potential non-estrogen-like drug candidate for prevention of postmenopausal obesity and fatty liver. The underlying mechanism might involve the inhibition of lipogenesis and promotion of triglycerides output in the liver, and the promotion of metabolism and mitochondrial functions of visceral white adipose tissue.

[Immune regulation effect of Chinese medicine of invigorating spleen and kidney detoxification on simian immunodeficiency virus-infected rhesus macaque].

To evaluate the effect of Chinese medicine of invigorating spleen and kidney detoxification on simian immunodeficiency virus-infected rhesus macaque. Eight SIV rhesus macaques of the same age were randomly divided into Chinese medicine of invigorating spleen and kidney detoxification group(hereinafter referred to as Chinese medicine group) and anti-virus drug(HAART) group. The traditional Chinese medicine and antiviral therapy were given for 8 weeks, and peripheral blood was collected for detection in every 4 weeks. The results showed that Chinese medicine of invigorating spleen and kidney detoxification could not obviously decrease plasma viral load as HAART, but it can increase CD4 number in peripheral blood, especially the CD4 naive cells, and increase the number of CD4 and CD8 cells, enhance the immune response to pathogens. Therefore, it delayed the occurrence and development of spleen deficiency to a certain extent, indicating that the medicine had immune regulation effect, with considerable clinical value and application prospects.

[Pharmacokinetic Effect of Aikeqing Granule by Different Medication Ways on Zidovudine in HAART of Rats].

OBJECTIVE: To study pharmacokinetic effect of Aikeqing Granule (AG) by different medication ways on zidovudine (AZT) in highly active antiretroviral therapy ( HAART) of rats. METHODS: Totally 36 rats were administered with corresponding medications by gastrogavage, group I [HAART: AZT 31.5 mg/kg +3TC 31.5 mg/kg + Efavirenz (EFV) 63.0 mg/kg], group II (HAART+AG525 mg/kg), group III (HAART and AG 525 mg/kg after a 2-h interval). Drug concentrations of AZT were determined by high performance liquid chromatography-mass spectroscopy (HPLC-MS) before HAART, and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12 h after HAART, respectively. Pharmacokinetic parameters [such as t1/2, Tmax, Cmax, AUCo-t, plasma clearance rate (CL)] were calculated by DAS2.0 Software. RESULTS: The-equation of linear regression of AZT was good, with the precision, coefficient of recovery, and stability definitely confirmed. AUC in group II and III was larger than that of group I. There was no statistical difference in t1/2, Tmax, Cmax, AUC0-12 h, or AUC0-∞ among groups (P > 0.05). CONCLUSION: AG combined HAART could enhance the Cmax of AZT.

[Experimental observation of SIVmac239 Chinese rhesus monkey model at sub-acute phase of AIDS].

OBJECTIVE: To observe T lymphocyte subsets and indicators of changes in viral load in sub-acute period in Chinese rhesus monkey model of AIDS SIVmac239. To explore Virology related index variation in sub-acute period of the Chinese rhesus monkey model of AIDS. METHOD: To replicate Chinese rhesus monkey model of AIDS, healthy Chinese rhesus monkey was inoculated with SIVmac239 viral strain. To observe changes in T lymphocyte subsets indexes and viral load after infection with the simian immunodeficiency virus (SIV) in sub-acute period on an animal model. The clinical symptoms of the animal model was recorded simultaneously. RESULT: During the 10 weeks after SIV acute infection, body weight and BMI index were relatively stable, the difference was not significant at all time points. Twelve monkeys were tested SIV positive by real-time PCR after three days of infection. On the 7th day after infection, 15 monkeys were tested SIV positive. Viral load increased rapidly, but reached a peak on the 10th-14th day after infection, then showed a level of volatility decline. T lymphocyte subsets showed significant changes, among them, CD3% and CD3 counts fluctuated upward trend and reached to the highest level in two weeks after infection; of CD4% and CD4 count changes were not synchronized, CD4% declined trend while the CD4 count was an increasing trend after the infection; of CD8% and CD8 counts fluctuate upward trend, and reached to a highest level in two weeks after infection ;the ratio of CD4/CD8 and the counts of CD4CD28 T cells decreased significantly in two weeks after infection; the former followed by a slow decline, the latter followed by a rapid rise. Three mouths after the infection 3 monkeys showed significant clinical symptoms. One of the rhesus monkeys had symptoms of diarrhea and two of them had reduced food intake. CONCLUSION: This experiments established standardization of Chinese Rhesus monkeys used in the research of AIDS and provide a detailed contents in the changes of sub-acute phase.

[Study on the regional features of Chinese medicine etiology and pathogenesis of AIDS].

OBJECTIVE: To analyze the differences in the Chinese medicine (CM) etiology and pathogenesis of AIDS. METHODS: A cross-sectional investigation study of AIDS patients and non-infected people was carried out in Henan, Guangdong and Xinjiang provinces respectively by questionnaire of clinical epidemiology and analyzed with frequencies of symptoms and signs combined with syndrome factors. The distribution differences of syndrome factors in the 3 provinces were compared. RESULTS: Totally 321 cases were investigated in the 3 provinces. As for the syndrome factors of AIDS, qi deficiency, blood deficiency, yin deficiency, yang deficiency, dampness evil, phlegm, qi stagnation, essence deficiency, and so on were dominated in the 3 provinces, but with their own features. For example, the scores of dampness evil were higher in Guangdong Province. Yin deficiency was dominated in Xinjiang Province. The scores of Henan Province were generally higher. As for the location of syndrome factors, Shen, Fei, Pi, and Gan were dominated in the 3 provinces. The score of Pi was the highest in Guangdong Province, while the score of Shen was the highest in Henan and Xinjiang provinces. CONCLUSIONS: AIDS has regional features in the nature and the syndrome factors of location in different provinces. It is necessary to take into consideration the regional factors when analyzing the pathogenesis of AIDS.

Traditional Chinese medicine etiology and pathogenesis of acquired immune deficiency syndrome in simian immunodeficiency virus-infected Chinese rhesus macaques.

OBJECTIVE: To investigate the traditional Chinese Medicine (TCM) etiology and pathogenesis of acquired immune deficiency syndrome (AIDS) by 18-month observation of Chinese rhesus macaques infected with simian immunodeficiency virus (SIV) mac239. METHODS: Thirty-five healthy Chinese rhesus macaques were divided into a model group (n = 30) and a control group (n = 5). The model was established by inoculating monkeys intravenously with SIVmac239. Changes in TCM symptoms after SIV infection within 18 months were then observed and recorded. Routine blood tests, SIV viral load, T-lymphocyte subsets, plasma triiodothyronine (T3), tetraiodothyronine (T4), adrenocorticotropic hormone (ACTH) and cortisol (Cor) were tested periodically during the experiment. RESULTS: During the acute infection period of SIV, model monkeys temporarily showed clinical symptoms such as diarrhea, dysphoria and slight weight loss. Decrease percentages of CD4+ T-lymphocytes were observed but levels of T3, T4, Cor, and ACTH were relatively unchanged. Monkeys in the model group during the early and middle periods of infection showed no obvious symptoms, except few monkeys exhibited transient diarrhea and reduced food intake. All variables at this stage showed normal fluctuations. In the middle period model group monkeys showed chronic and persistent diarrhea, weight loss, reduced food intake and low levels of T3 and Cor. In the late period, symptoms including emaciation, weight loss, listlessness, crouching in corners and low levels of T3 appeared. CONCLUSION: The results suggest that the rhesus monkey SIV/SAIDS model can be applied to research on TCM etiology and pathogenesis of AIDS. According to this model, the etiology of disease is the SIV virus. The pathogenesis manifests as the invasion of SIV virus, incubation of the virus, balance between virus and healthy "Qi", damage to spleen and kidney as the disease progressed, exhaustion of vitality and finally the failure of five zang and six fu organs.

[Traditional Chinese medicine syndrome factors of patients with HIV infection or AIDS in China].

OBJECTIVE: To study the characteristics of traditional Chinese medicine (TCM) syndrome factors of patients from different areas of China with human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS). METHODS: A cross-sectional investigation study was conducted in Henan, Guangdong and Yunnan Provinces and Xinjiang Uygur Autonomous Region of China from October 2008 to August 2010. Based on literature review and expert opinion, a clinical questionnaire of TCM syndromes was drawn up. This survey was carried out after the investigators were professionally trained. Wenfeng III Auxiliary Diagnosis and Treat System of TCM was used to analyze the frequencies of AIDS patients' signs and symptoms with scores above 70 of syndrome factors respectively. Based on this work, syndrome factors of AIDS were analyzed in different areas. RESULTS: There were 608 HIV/AIDS cases investigated from October 2008 to August 2010 in total; among them, 276 cases were from Henan, 126 cases from Guangdong, 120 cases from Xinjiang and 86 cases from Yunnan. The results of syndrome factor analysis indicated that the syndromes of four provinces were similar. HIV/AIDS patients in the four areas exhibited qi deficiency, blood deficiency, yin deficiency, yang deficiency, dampness, phlegm, qi stagnation and essence deficiency syndromes. Patients in each area also had their own characteristics, such as that the scores of dampness of Guangdong and yin deficiency of Xinjiang were higher than the other syndromes, whereas the scores of Henan Province were higher than the other areas. AIDS patients had higher scores of syndromes than HIV-infected patients. CONCLUSION: HIV/AIDS patients from different areas had similar syndrome elements. The theory of "AIDS toxin injuring primordial qi" can sum up the TCM etiology and pathogenesis of HIV/AIDS.

A new 3-benzylchroman derivative from Sappan Lignum (Caesalpinia sappan).

3'-Deoxy-4-O-methylepisappanol, a new 3-benzylchroman derivative, was isolated from Sappan Lignum, together with thirteen known chemical compounds identified as protosappanin A, sappanchalcone, sappanone B, palmitic acid, (+)-(8S,8'S)-bisdihydrosiringenin, brazilein, 3-deoxysappanchalcone, (+)-lyoniresinol, 3-deoxysappanone B, protosappanin B, isoprotosappanin B, 3'-O-methylbrazilin and brazilin, respectively. Among these known compounds, this is the first time that (+)-(8S,8'S)-bisdihydrosiringenin was obtained from the family Caesalpiniaceae.

Tenacigenin B derivatives reverse P-glycoprotein-mediated multidrug resistance inHepG2/Dox cells.

Tenacissimoside A (1) and 11alpha-O-benzoyl-12beta- O-acetyltenacigenin B (2), two derivatives of tenacigenin B (3) from the plant Marsdenia tenacissima, reversed multidrug resistance in P-glycoprotein (Pgp)-overexpressing multidrug-resistant cancer cells. The sensitivity of HepG2/Dox cells to the antitumor drugs doxorubicin, vinblastine, puromycin, and paclitexel was increased by 18-, 10-, 11-, and 6-fold by 20 microg/mL (or 25 microM) of 1 and 16-, 53-, 16-, and 326-fold by 20 microg/mL (or 39 microM) of 2, respectively. A preliminary mechanistic study has suggested that 1 might modulate Pgp-mediated multidrug resistance through directly interacting with the Pgp substrate site.

[Blood lipid-regulation of stilbene glycoside from polygonum multiflorum].

OBJECTIVE: To study lipid-regulating action of 2, 3, 5, 4'-tetrahydroxy stilbene-2-O-beta-D-glucopyranoside (TSG) from Polygonum multiflorum on experimental model hyperlipidemic rats. METHOD: TSG 90 and 180 mg x kg(-10 x d(-1), atorvastatin mg kg(-1) x d(-1) and saline 2 mL x d(-1) were administered to hyperlipidemic rats. Groups of rats were determined and compared with those of saline group. The LDLR and HMGR mRNA expression were also detected. RESULT: TSG significantly reduced serum TC and LDL-C level and atherosclerosis index, increased the expression of LDLR in the liver cells. CONCLUSION: TSG, which shows effects and mechanism in part like atorcastatin, is a major constituent with blood-lipid regulating effect of P. multiflorum and can be explored as a potent medication for hyperlipidemia. Effects on LDL-C and AI, as well as on gene expression of TSG were first reported.

[A randomized comparative study of naphtoquine, mefloquine and artsunate in the treatment of falciparum malaria].

OBJECTIVE: To evaluate the efficacy and safety of naphtoquine, compared with mefloquine and artesunate in the treatment of falciparum malaria. METHOD: Ninety patients with falciparum malaria were randomly allocated to 3 groups, including naphtoquine, mefloquine and artesunate group. In the naphtoquine group, thirty patients were prescribed single daily dosage of 1,000 mg for one day. In the mefloquine group, equal patients were treated with single dosage of 750 mg. Another thirty patients in the artesunate group were given total dosage of 600 mg for five days and doubling dosage on the first day. RESULT: In all three groups, symptoms were well controlled. The average fever-subsidence time in naphtoquine group was 30 h +/- 16 h and approximate that in mefloquine group (24 h +/- 15 h, P>0.05), but was longer than that in naphtoquine group (18 h +/- 9 h, P<0.01). The average parasite-clearance time in naphtoquine group (98 h +/- 28 h) is longer than that in mefloquine group (57 h +/- 20 h, P<0.01) and that in artesunate group (43 h +/- 17 h, P<0.01). At the end of 28-day clinical trail, the curative ratio in naphtoquine group was the highest (96.7%), and was significantly higher than that in mefloquine group (76.7%, P<0.05) and artesunate group (73.3%, P<0.05). Slight nausea and vomiting were observed in few patient in three groups. CONCLUSION: Although the average fever-subsidence time and the parasite-clearance time of naphtoquine at single 24-hour dosage of 1,000 mg were longer than those of mefloquine and artesunate, the 28-day curative ratio of naphtoquine was higher than that of mefloquine and artesunate. So we recommend that the combination of artemisinin, which is a rapid action antimalarial, and naphtoquine or mefloquine, which are longterm action antimalarial, would contribute to promoting efficacy, shorting the period of treatment and delaying occurrence of drug resistance.