Tsaokoflavanols A1-J1: Flavanol-fatty alcohol hybrids with HPL inhibitory activity from Amomum tsao-ko.

Ten previously undescribed compounds were isolated from the fruits of Amomum tsao-ko (Zingiberaceae), including nine undescribed flavanol-fatty alcohol hybrids (1-6, 10-11, 13), and a flavanol-monoterpenoid hybrid (14), along with seven known flavanol hybrids (7-9, 12, 15-17). The structures of these compounds were determined using various analyses, such as HRESIMS, 1D/2D NMR, and ECD calculations. In terms of biological activity, compounds 1, 2, 5, and 6 exhibited inhibitions of human pancreatic lipase (HPL), with IC50 values ranging from 0.017 to 0.193 mM. Some of these values were found to be stronger than that of the positive control, orlistat (IC50, 0.067 mM). Molecular docking studies were also conducted to investigate the interactions between these compounds and HPL. The docking simulations revealed the importance of the orientation of the 3,4-dihydroxyphenyl in binding with HPL. Additionally, compound 9 demonstrated cytotoxicity against HepG2, with a CC50 value of 14.96 ± 0.62 µM as determined by the MTT assay. Flow cytometry analysis indicated that compound 9 induced apoptosis in HepG2 cells. Western blot results showed an up-regulation of apoptosis-related proteins, such as p53 protein, Bax and Caspase-3 proteins, while the expression of Bcl-2 protein was down-regulated.

A case-control study and systematic review of the association between glutathione S-transferase genes and chronic kidney disease.

Background: GSTM1 deletion was reported to be associated with CKD progression in cohort studies. However, the results of case‒control studies were conflicting. The association between GST genes and CKD progression needs to be studied in China. Therefore, we conducted this case‒control study and systematic review for Southwest China to outline the association between GST genes and CKD. Methods: CKD patients and healthy controls were enrolled from June 1, 2022 to 1 August 2022. Reported case‒control studies were identified by searching databases until 1 September 2022 for meta-analysis. Results: Significant associations were found between deletions of GSTM1 and GSTT1 and CKD risk (all P < 0.01) but not in GSTP1 rs1695 (all P > 0.05) in Southwest China. Then, we conducted a meta-analysis on 30 studies and found positive associations between deletions of GSTM1 and GSTT1 and CKD risk (all P < 0.01) but failed to find associations in GSTP1 rs1695 (all P > 0.05). Stratification analysis for ethnicity only showed a significant association in Southern Asia (P < 0.05) but not in Eastern Asia or other populations. This was different from our case‒control results. The current evidence was influenced by study quality and PCR method but not by control selection. Given the different stages of CKD patients, a subanalysis of disease stages was performed, and the results remained positive. Interestingly, we found no significant associations between DM-CKD and GST genes, which should be interpreted with caution. Conclusion: We found that GSTM1 and GSTT1 null genotypes were risk factors for CKD in China. The results of the meta-analysis were somewhat different from our results. We considered that antioxidant therapy might be useful for the treatment of these patients.

NARFL deficiency caused mitochondrial dysfunction in lung cancer cells by HIF-1α-DNMT1 axis.

NARFL was reported to be a component of cytosolic iron-sulfur cluster assembly pathway and a causative gene of the diffused pulmonary arteriovenous malformations (dPAVMs). NARFL knockout dramatically impaired mitochondrial integrity in mice, which might promote mitochondrial dysfunction and lead to worse survival rate of lung cancer. However, the underlying molecular mechanism of NARFL deficiency in non-small cell lung cancer (NSCLC) is unknown. Knockdown assay was performed in A549 and H1299 cells. The protein levels of HIF-1α and DNMT1 were measured, and then Complex I activity, mtDNA copy numbers and mRNA levels of mtND genes were determined. Cisplatin resistance and cell proliferation were conducted using CCK8 assay. Cell migration and invasion were detected using wound heal assay and transwell assay. Survival analysis of lung cancer patients and KM plotter database were used for evaluating the potential value of NARFL deficiency. NARFL protein was expressed in two cell lines and knockdown assay significantly reduced its levels. Knockdown NARFL increased the protein levels of HIF-1α and DNMT1, and downregulated the mRNA levels of ND genes, mitochondrial Complex I activity, mtDNA copy number, and ATP levels. The mitochondrial dysfunction caused by NARFL deficiency were ameliorated by siHIF-1α and DNMT1 inhibitor. Knockdown NARFL increased the drug resistance and cell migration, and siHIF-1α reversed this effect. Moreover, NSCLC patients with NARFL deficiency had a poor survival rate using a tissue array and KM plotter database, and it would be a target for cancer prognosis and treatment. NARFL deficiency caused dysregulation of energy metabolism in lung cancer cells via HIF-1α-DNMT1 axis, which promoted drug resistance and cell migration. It provided a potential target for treatment and prognosis of lung cancer.

Structure-Based Molecular Networking for the Discovery of Anti-HBV Compounds from Saussurea lappa (Decne.) C.B Clarke.

It is a crucial to find target compounds in natural product research. This study presents a concept of structure-guided isolation to find candidate active molecules from herbs. We establish a process of anti-viral sesquiterpene networking. An analysis of the networking suggested that new anti-HBV sesquiterpene may be attributable to eudesmane-, guaiane-, cadinane-, germacane- and bisabolane-type sesquiterpenes. In order to evaluate the efficiency of the structure-based molecular networking, ethanol extract of Saussurea lappa (Decne.) C.B Clarke was investigated, which led to the isolation of two guaiane-type (1 and 14), ten eudesmane-type (2-5 and 8-13), two chain (6 and 7) and one germacrane-type (15) sesquiterpenes, including seven new ones, lappaterpenes A-G (1-7), which are reported on herein. The absolute configurations of the new compounds were established by coupling constants, calculated ECD and ROESY correlations, as well as comparisons of optical rotation values with those of known compounds. The absolute configuration of compound 2 was further confirmed by X-ray diffraction. Compounds 1-15 were evaluated for their potency against hepatitis B virus. Compounds 4, 6, 7 and 9 showed effect on HBsAg with inhibition ratios of more than 40% at 30 µM concentrations. Compounds 14 and 15 inhibited HBsAg secretion with the values of IC50 0.73 ± 0.18 and 1.43 ± 0.54 µM, respectively. Structure-based molecular networking inspired the discovery of target compounds.