Sesquiterpenoids and steroids from Eupatorium fortunei and their inhibitory effects on NO production.

Two heterodimers including a clovane-phenylpropanoid hybrid (1) and a clovane-menthane hybrid (2), five linear sesquiterpenoids incorporating a tetrahydrofuran ring (3-6 & 8), and four steroids (7 & 9-11), were separated from the ethanolic extract of a well-known aromatic and medicinal herb Eupatorium fortunei. Their structures were characterised by detailed analyses of spectroscopic data and comparison with known analogues, with seven (1-7) of them being described for the first time. The hybrids 1 and 2 represent the first examples of clovane type sesquiterpenoids hybridising with other class of natural products, and compounds 3-6 and 8 are first linear sesquiterpenyl constituents reported from the title species. All the isolates were evaluated for their inhibitory effect on the NO production induced by LPS in murine RAW264.7 macrophage cells, and 1, 7, 10 and 11 exhibited moderate activity with IC50 values in the range of 24.4-43.5 µM.

Anti-inflammatory Polyketides from an Endophytic Fungus Chaetomium sp. UJN-EF006 of Vaccinium bracteatum.

Seven new polyketides including three chromone derivatives (1-3) and four linear ones incorporating a tetrahydrofuran ring (4-7), along with three known compounds (8-10), were obtained from the fermentation of an endophytic fungus (Chaetomium sp. UJN-EF006) isolated from the leaves of Vaccinium bracteatum. The structures of these fungal metabolites have been elucidated by spectroscopic means including MS, NMR and electronic circular dichroism. A preliminary anti-inflammatory screening with the lipopolysaccharide (LPS) induced RAW264.7 cell model revealed moderate NO production inhibitory activity for compounds 1 and 4. In addition, the expression of three LPS-induced inflammatory factors IL-6, iNOS and COX-2 was also blocked by 1 and 4.

Design, synthesis, and evaluation of dual-target inhibitors for the treatment of Alzheimer's disease.

Aß1-42 and acetylcholinesterase (AChE) are two key therapeutic targets for Alzheimer's disease (AD). The purpose of this study is to develop a dual-target inhibitor that inhibits both of these targets by fusing the chemical structure of baicalein and donepezil. Among them, we modified the structure of baicalein to arylcoumarin, synthesized three kinds of structural compounds, and evaluated their biological activities. The results showed that compound 3b had the strongest inhibitory effect on AChE (IC50 = 0.05 ± 0.02 µM), which was better than those of donepezil and baicalein. In addition, compound 3b has a strong ability to inhibit the aggregation of Aß1-42 and protect nerve cells, and it can also penetrate the blood-brain barrier well. Using a zebrafish behavioral analyzer test, it was found that compound 3b can alleviate the behavioral effects of AlCl3-induced zebrafish larval movement retardation, which has a certain guiding significance for simulating the movement disorders of AD patients. In summary, compound 3b is expected to become a multifunctional agent for treating and alleviating the symptoms of AD patients.

Synthesis and activity of arylcoumarin derivatives with therapeutic effects on diabetic nephropathy.

In the literature, daidzein has been reported to exhibit cardiovascular protective effects and hypoglycemic activity in mice. We sought to design and synthesize a novel compound, SJ-6, an analog of daidzein, with improved hypoglycemic properties. Although SJ-6 demonstrated favorable hypoglycemic effects, its pharmacokinetic limitations prompted us to design and synthesize prodrugs of SJ-6. We conducted a comprehensive evaluation of the prodrugs, including in vitro and in vivo studies, such as cytotoxicity, absorption, distribution, metabolism, excretion, and toxicity (ADMET) simulation analysis, in vitro blood-brain barrier (BBB) permeability evaluation, compound effect on insulin resistance, oral glucose tolerance test (OGTT), in vivo plasma concentration testing, acute toxicity test in rats, and long-term gavage administration experiment. Furthermore, we examined the antidiabetic nephropathy activity of our lead compound, compound 10, which demonstrated superior efficacy compared with the positive control drug, metformin hydrochloride. Our findings suggest that compound 10 represents a promising lead compound for the prevention and treatment of diabetic nephropathy.

Structurally Diverse Sesquiterpenoids with NO Production and α-Glucosidase Inhibitory Activities from the Fruits of Schisandra chinensis.

Chemical fractionation of the AcOEt partition, generated from the EtOH extract of the fruits of Schisandra chinensis, afforded a series of sesquiterpenyl constituents including two new cadinanes, a new eudesmane, two new widdranes (a handling artefact and a new natural product), a new bisabolane and two new natural cuparane enantiomers, along with 15 known structurally related analogs. Structures of the new compounds were unambiguously characterized by interpretation of detailed spectroscopic data including ESI-MS and 1D/2D NMR, with their absolute configurations being established by electronic circular dichroism (ECD) calculation and induced ECD experiment. The inhibitory effects of all the isolates against α-glucosidase and lipopolysaccharide (LPS) induced nitric oxide (NO) production in murine RAW264.7 macrophages, as well as their antibacterial and cytotoxic potential, were evaluated, with selective compounds showing moderate α-glucosidase and NO inhibitory activity. Notably, canangaterpene III exhibited the most significant NO inhibitory effect with an IC50 value of 31.50±1.49 µM.

Bioactivity and mechanisms of flavonoids in decreasing insulin resistance.

Flavonoids are ubiquitous compounds in nature and are found in many Chinese herbal medicines. Due to their biological activity, flavonoids show potential for decreasing insulin resistance (IR), thereby delaying the progression of diabetes and accompanying metabolic syndromes. This review focuses on the mechanisms of flavonoids decreasing IR: (1) the interaction between flavonoids and target proteins of the insulin signalling pathway; (2) bioactivities of flavonoids, such as anti-inflammatory, lipid-lowering and antioxidant. Meanwhile, we summarise the structural characteristics, structure activity relationships and biological activity of flavonoids, providing evidence for their potential in the treatment of IR. Here, we also analyse the potential and limitations of their therapeutic use.

3-Arylcoumarin inhibits vascular calcification by inhibiting the generation of AGEs and anti-oxidative stress.

OBJECTIVE: This work aims to screen drugs for preventing and treating vascular calcification. Method: We screened a series of 3-arylcoumarins for the detection of vascular calcification-associated factors using human aortic vascular smooth muscle cells. RESULTS: We found that compounds 14 and 32 significantly inhibited alkaline phosphatase (ALP) activity similar to aminoguanidine hydrochloride (AGH) in a cellular model of AGEs-induced calcification. We also found that compounds 14 and 32 could significantly decrease the levels of factors such as AGEs, intracellular calcium ions, and total ROS in the calcified cell model. Further study indicates that compound 14 could significantly inhibit the expression of P-ERK1/2, PKC, NF-κB, RAGE and OPN proteins and increased the expression of SM22-α and PPAR-γ proteins in the calcified cells. CONCLUSION: We speculate that compound 14 inhibits vascular calcification by inhibiting oxidative stress and inhibiting AGEs production, suggesting that 3-arylcoumarin derivatives are potential candidates for the treatment of vascular calcification.

Vascular calcification is a process similar to bone formation, which is highly adjustable and active. Currently, there are no specific drugs to delay or reverse vascular calcification. Through the screening of 44 coumarin compounds synthesised by our group, compound 14 was obtained to dose-dependently inhibit the calcification of vascular smooth muscle cells without affecting the normal proliferation of cells, decreasing the intracellular calcium concentration, inhibiting the activity of ALP enzyme. In conclusion, the calcium lowering effect of compound 14 is a potential candidate for drugs for the treatment of vascular calcification.

Research progress of coumarins and their derivatives in the treatment of diabetes.

Diabetes is a group of metabolic diseases characterised by chronic hyperglycaemia caused by multiple causes, which is caused by insulin secretion and/or utilisation defects. It is characterised by increased fasting and postprandial blood glucose levels due to insulin deficiency or insulin resistance. It is reported that the harm of diabetes mainly comes from its complications, and the cardiovascular disease caused by diabetes is the primary cause of its harm. China has the largest number of diabetic patients in the world, and the prevention and control of diabetes are facing great challenges. In recent years, many kinds of literature have been published abroad, which have proved that coumarin and its derivatives are effective in the treatment of diabetic complications such as nephropathy and cardiovascular disease. In this paper, the types of antidiabetic drugs and the anti-diabetic mechanism of coumarins were reviewed.

Caloric restriction induced epigenetic effects on aging.

Aging is the subject of many studies, facilitating the discovery of many interventions. Epigenetic influences numerous life processes by regulating gene expression and also plays a crucial role in aging regulation. Increasing data suggests that dietary changes can alter epigenetic marks associated with aging. Caloric restriction (CR)is considered an intervention to regulate aging and prolong life span. At present, CR has made some progress by regulating signaling pathways associated with aging as well as the mechanism of action of intercellular signaling molecules against aging. In this review, we will focus on autophagy and epigenetic modifications to elaborate the molecular mechanisms by which CR delays aging by triggering autophagy, epigenetic modifications, and the interaction between the two in caloric restriction. In order to provide new ideas for the study of the mechanism of aging and delaying aging.