Indole Alkaloids from the Leaves of Nauclea officinalis.

Three new indole alkaloids, named naucleamide G (1), and nauclealomide B and C (5 and 6), were isolated from the n-BuOH-soluble fraction of an EtOH extract of the leaves of Nauclea officinalis, together with three known alkaloids, paratunamide C (2), paratunamide D (3) and paratunamide A (4). The structures with absolute configurations of the new compounds were identified on the basis of 1D and 2D NMR, HRESIMS, acid hydrolysis and quantum chemical circular dichroism (CD) calculation. According to the structures of isolated indole alkaloids, their plausible biosynthetic pathway was deduced.

Author Correction: Cyclocarya paliurus tea leaves enhances pancreatic ß cell preservation through inhibition of apoptosis.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Cyclocarya paliurus Leaves Tea Improves Dyslipidemia in Diabetic Mice: A Lipidomics-Based Network Pharmacology Study.

Hyperlipidemia and hepatic steatosis afflict over 75% of patients with type 2 diabetes, causing diabetic dyslipidemia. Cyclocarya paliurus (CP) leaf is a herbal tea which has long been consumed by the Chinese population, particularly people suffering from obesity and diabetes. CP appears to exhibit a hypolipidemic effect in lipid loaded mice (Kurihara et al., 2003), although the detailed mechanisms and active ingredients for this hypolipidemic effect have not yet been answered. In this study, we investigated the beneficial effects of CP and predicted the mechanisms by utilizing lipidomics, serum-pharmacochemistry and network pharmacology approaches. Our results revealed that serum and hepatic levels of total triglyceride (TG), total cholesterol (T-CHO), low-density lipoproteins (LDL) and high-density lipoproteins (HDL), as well as 30 lipids including cholesterol ester (CE), diglyceride (DG), phosphatidylethanolamine (PE), phosphatidylcholine (PC), and sphingomyelin (SM) in CP-treated mice were improved in comparison with untreated diabetic mice. In parallel, 14 phytochemical compounds of CP were determined in mice serum after CP administration. Mechanistically, the network pharmacology analysis revealed the predicted targets of CP's active ingredients ALOX12, APP, BCL2, CYP2C9, PTPN1 and linked lipidome targets PLD2, PLA2G(s), and PI3K(s) families could be responsible for the CP effects on diabetic dyslipidemia. In conclusion, this study revealed the beneficial effects of CP on diabetic dyslipidemia are achieved by reducing accumulation of hepatic lipid droplets and regulating circulatory lipids in diabetic mice, possibly through PI3K signaling and MAPK signaling pathways. GRAPHICAL ABSTRACTWork flow of the evaluation of the effects and mechanisms of Cyclocarya paliurus leaves tea on dyslipidemia in diabetic mice.

Cyclocarya paliurus tea leaves enhances pancreatic ß cell preservation through inhibition of apoptosis.

Leaves of Cyclocarya paliurus are a sweet tea traditionally used to treat obesity and diabetes in China. However, its protective mechanisms against hyperglycemia remains unclear. Here, we demonstrate that the extract of C. paliurus leaves significantly decreased body loss, food intake and blood glucose level, and increased blood insulin level, ß-cell number and insulin-producing ß cells in high-fat diet-low dose STZ-induced diabetic mice. In vivo and in vitro studies also showed the extract of C. paliurus leaves significantly inhibited pancreatic ß cell apoptosis by suppressing the expression of caspase 8, caspase 9 and cleaved caspase-3, as well as Bax/Bcl-2 ratio, down-regulating p38, ERK and JNK phosphorylation, and up-regulating Akt phosphorylation. These effects were significantly enhanced by inhibitor p-38 or ERK or JNK, and counteracted by inhibitor of PI3K. In addition, the extract of C. paliurus leaves also significantly improved hepatic steatosis, nephropathy and cardiac hypertrophy of diabetic mice. Taken together, these results provide the insight into the effects of C. paliurus leaves on pancreatic ß cell preservation in standing glucolipotoxicity. Therefore, C. paliurus tea leaves may be used as a new remedy for diabetes through enhancing pancreatic ß cell preservation by inhibiting ß cell apoptosis.

The antiviral effects of acteoside and the underlying IFN-γ-inducing action.

There are many herbal teas that are found in nature that may be effective at treating the symptoms and also shortening the duration of viral infections. When combating viral infections, T lymphocytes are an indispensable part of human acquired immunity. However, studies on the use of natural products in stimulating lymphocyte-mediated interferon-gamma (IFN-γ) production are very limited. In this study, we found that acteoside, a natural phenylpropanoid glycoside from Kuding Tea, enhanced IFN-γ production in mouse lymphocytes in a dose-dependent manner, particularly in the CD4+ and CD8+ subsets of T lymphocytes. To this end, we suggest that the antiviral activity of acteoside was highly correlated to its inducing ability of IFN-γ production. Mechanistically, the activation of T-bet enhanced the promoter of IFN-γ and subsequently resulted in an increased IFN-γ production in T cells. Collectively, we have found a natural product with the capacity to selectively enhance mouse T cell IFN-γ production. Given the role of IFN-γ in the immune system, further studies to clarify the role of acteoside in inducing IFN-γ and prevention of viral infection are needed.

Anti-influenza virus effects of crude phenylethanoid glycosides isolated from ligustrum purpurascens via inducing endogenous interferon-γ.

ETHNOPHARMACOLOGICAL RELEVANCE: Ligustrum purpurascens Y.C. Yang (Oleaceae) is traditionally recorded as "Ku Ding Cha", a kind of functional tea in southern China for about two thousand years, which has been reported with sore throat alleviating and pathogenic heat expelling effects. However, there are no scientific studies demonstrating its antiviral activity. THE AIM OF THE STUDY: This study is aimed at investigating the anti-influenza virus effects of phenylethanoid glycosides isolated from L. purpurascens (LPG) as well as its corresponding mechanisms. MATERIALS AND METHODS: In vitro, hemagglutination assay was employed to detect the influenza virus titer; In vivo, C57BL/6J mice were given oral administration of LPG (100mg/kg, 300mg/kg, 900mg/kg) or ribavirin (100mg/kg) once daily for 5 successive days. Meanwhile, on the second day, mice were infected intranasally (i.n.) with A/FM/1/47 H1N1 virus. Mice survival rate and other clinical index were monitored for 15 days. Infected mice were sacrificed to measure the lung lesion and stained with hematoxylin-eosin. Flow cytometry analyses spleen lymphocytes and interferon-γ (IFN-γ) level. The IFN-γ knockout mice (IFN-γ(-/-) mice, C57BL/6J) which had been verified lacking IFN-γ through Western Blot, were applied in the death-protection test to identify the role of IFN-γ played in LPG antiviral effect. RESULTS: In vitro, LPG at 0.5mg/ml inhibited Influenza A Virus H1N1 type (H1N1) infection of MDCK cells. In vivo, LPG at 300 and 900mg/kg significantly decreased the mouse lung index (p<0.05), alleviated influenza-induced lethality and clinical symptoms, and therefore enhanced mouse survival (p<0.05). More detailed experiments demonstrated that antiviral cytokine IFN-γ was involved in the antiviral effect of LPG. Flow cytometric analysis revealed that LPG (900mg/kg) significantly induced secretion of IFN-γ by splenic CD4(+) and CD8(+) cells (p<0.05). Moreover, LPG (900mg/kg) protected wild-type C57BL/6J mice from H1N1 injury, whereas LPG-mediated survival protection disappeared in IFN-γ(-/-) mice. CONCLUSION: These results suggest that up-regulating endogenous IFN-γ by LPG may represent a novel therapeutic approach for H1N1 infection.