Ameliorating Effect and Potential Mechanism of Camellia Oil on Constipated Mice

Constipation is a global epidemic. To evaluate the ameliorating effect of camellia oil on constipation,two slowtransit costive mice models were established by water deprivation or sucralfate gavage. Administration of camellia oil（ 4. 0 and 8. 0 mL/kg/day） significantly shortened the defecation time,increased defecation mass and fecal water content,with efficacies comparable to that of hemp seed oil. Intestinal propulsion test showed that camellia oil significantly enhanced the propelling rates of the charcoal powder in the intestine. Meanwhile,camellia oil also significantly decreased the serum levels of nitric oxide（ NO）,nitric oxide synthase（ NOS） and vasoactive intestinal peptide（ VIP） and increased serum substance P in costive animals. These results suggested that camellia oil can largely relieve slowtransit constipation and enhance the gastrointestinal motility through modulation of serum gastrointestinal motility key factors such as NO,NOS and VIP and substance P.

Proteomics analysis on hypolipidemic mechanisms of total phenylpropanoid glycosides from Ligustrum robustum(Roxb.) Blume in hamsters fed a high fat diet

OBJECTIVE To explore the hypolipidemic mechanisms of the total phenylpropanoid glycosides fromLigustrum robustum(Roxb.) Blume(LRTPG) in hamsters using proteomics technique.METHODS The hamsters were fed with a high fat diet to induce hyperlipidemia.Then LRTPG of high(1.2 g·kg^(-1)),medium(0.6 g·kg^(-1)) and low(0.3 g·kg^(-1)) doses were administrated daily for 4 weeks.Then the concentrations of plasma and hepatic lipids were determined using enzymic methods.The total protein was extracted from livers of the model group and the group treated with the high dose of LRTPG for label-free quantitative proteomics.RESULTS LRTPG significantly reduced the concentrations of plasma and hepatic lipids in hamsters fed a high fat diet.The proteomics data showed that a total of 2231 proteins were identified,and 549 proteins were found to be differentially expressed between the model group and the group treated with LRTPG.Among the 549 proteins,93 proteins were up-regulated and 59 proteins were down-regulated,and 397 proteins were absent or not.And some of these proteins were much related to the lipid metabolism.Further,gene ontology(GO) analysis indicated metabolic process,transport,oxidation-reduction process,phosphorylation,signal transduction,lipid metabolic process were the main biological processes that those differentially expressed proteins participated.KEGG pathway analysis showed that those proteins were involved in several metabolic pathways including oxidative phosphorylation,non-alcoholic fatty liver disease(NAFLD),PI3K-Akt signaling pathway,cAMP signaling pathway,cGMP-PKG signaling pathway.CONCLUSION The proteomics study could provide valuable clues to help us to understand the hypolipidemic mechanisms of LRTPG much better.

Modulative effect of Physalis alkekengi on both gut bacterial and fungal micro-ecosystem

Objective: Gut microbiome is an intricate micro-ecosystem mediating the human health and drug efficacy. Physalis alkekengi(PAL) is an edible and time-honored traditional Chinese medicine. Several pharmacological effects of PAL have been verified and gut bacteria are implied in its therapeutic actions.However, the detailed modulation of PAL on gut bacterial species and on gut fungi remains largely unknown. We, therefore, designed a preliminary experiment in normal mice to reveal the modulation effect of PAL on both gut bacteria and fungi, and explore the interaction between them.Methods: Herein, the aqueous extract of PAL was orally administrated to normal C57BL/6 mice for four weeks. The full-length 16S rRNA and ITS1/2 gene sequencing were explored to detect the taxa of gut bacteria and gut fungi after PAL treatment, respectively.Results: Oral administration of PAL notably enriched anti-infammatory bacterial species such as Duncaniella spp. and Kineothrix alysoides, whereas decreased pro-infammatory species such as Mucispirillum schaedleri. Simultaneously, PAL increased the abundance of gut fungi Aspergillus ochraceus,Cladosporium sp. and Alternaria sp., and decreased Penicillium janthinellum. Correlation network analysis identified two co-existing microbial groups(groups 1 and 2) that were negatively associated with each other. The group 1 comprised PAL-enriched bacteria and fungi, while group 2 was mainly normal chow-enriched bacteria and fungi. In group 1, Antrodia monomitica, Aspergillus clavatus, Mortierella kuhlmanii and Sarcinomyces sp. MA 4787 were positively correlated with Bifidobacterium globosum,Romboutsia ilealis and so on. In group 2, Chaetomium subspirilliferum, Septoria orchidearum and Cephaliophora tropica were positively related to Lactobacillus spp.Conclusion: Altogether, this preliminary study first demonstrated the modulation effect of PAL on both gut bacteria and gut fungi, which may shed light on the elucidation of PAL’s pharmacological mechanism.

Equisetin is an anti-obesity candidate through targeting 11β-HSD1

Obesity is increasingly prevalent globally, searching for therapeutic agents acting on adipose tissue is of great importance. Equisetin(EQST), a meroterpenoid isolated from a marine sponge-derived fungus, has been reported to display antibacterial and antiviral activities. Here, we revealed that EQST displayed anti-obesity effects acting on adipose tissue through inhibiting adipogenesis in vitro and attenuating HFD-induced obesity in mice, doing so without affecting food intake, blood pressure or heart rate.We demonstrated that EQST inhibited the enzyme activity of 11β-hydroxysteroid dehydrogenase type 1(11β-HSD1), a therapeutic target of obesity in adipose tissue. Anti-obesity properties of EQST were all offset by applying excessive 11β-HSD1’s substrates and 11β-HSD1 inhibition through knockdown in vitro or 11β-HSD1 knockout in vivo. In the 11β-HSD1 bypass model constructed by adding excess11β-HSD1 products, EQST’s anti-obesity effects disappeared. Furthermore, EQST directly bond to11β-HSD1 protein and presented remarkable better intensity on 11β-HSD1 inhibition and better efficacy on anti-obesity than known 11β-HSD1 inhibitor. Therefore, EQST can be developed into anti-obesity candidate compound, and this study may provide more clues for developing higher effective 11β-HSD1 inhibitors.

Cordycepin promotes browning of white adipose tissue through an AMP-activated protein kinase(AMPK)-dependent pathway

Obesity is a worldwide epidemic. Promoting browning of white adipose tissue(WAT)contributes to increased energy expenditure and hence counteracts obesity. Here we show that cordycepin(Cpn), a natural derivative of adenosine, increases energy expenditure, inhibits weight gain, improves metabolic profile and glucose tolerance, decreases WAT mass and adipocyte size, and enhances cold tolerance in normal and high-fat diet-fed mice. Cpn markedly increases the surface temperature around the inguinal WAT and turns the inguinal fat browner. Further investigations show that Cpn induces the development of brown-like adipocytes in inguinal and, to a less degree, epididymal WAT depots. Cpn also increases the expression of uncoupling protein 1(UCP1) and other thermogenic genes in WAT and3T3-L1 differentiated adipocytes, in which AMP-activated protein kinase(AMPK) plays an important role. Our results provide novel insights into the function of Cpn in regulating energy balance, and suggest a potential utility of Cpn in the treatment of obesity.

Gut Microbiota Brings a Novel Way to Illuminate Mechanisms of Natural Products in vivo

Poor bioavailability and undefined major/direct targets are two major obstacles for herbal medicines and natural products（NPs） to elucidate their precise mechanisms in vivo. Gut microbiota is an important bridge between eukayotic body and environment, which can interact with a majority of medicines with poor bioavailability and mediate their in vivo pharmacological activities. There are two main modes through which gut microbiota may mediate the pharmacological effects of NPs. First, gut microbiota catabolizes the NPs in herbal medicines into secondary metabolites with higher bioavialability and/or higher activity, facilitating the NPs enter circulation and exert beneficial impact at the pathological spot. Second, herbal medicines and NPs can favorably shift the compositional structure of gut microbiota, thereby performing remote functions to diseased organs/tissues via the systemic impaction of gut microbiota. In this review, the potential pathways were summarized through which gut microbes facilitate the pharmacological functions of herbal medicines and NPs and highlight the significance of gut microbiota in clarifying the in vivo mechanisms of herbal medicines and NPs.