Comprehending the mechanism of catechins against α-glucosidase by multispectral data and their antidiabetic effects in vivo.

Diabetes mellitus (DM) is a common metabolic disorder characterized by the elevated blood glucose levels. Catechins comprising four isomers, (+)-catechin [(+)CT], (-)-catechin [(-)CT], (+)-epicatechin [(+)ECT] and (-)-epicatechin [(-)ECT], are a family of flavanols widespread in natural sources. In this study, four catechins were extensively evaluated against diabetes-related enzymes, of which (+)CT (IC = 63.

Asymmetric total synthesis of amovillosumins A and B and their hypoglycemic and anti-inflammatory activities.

Motivated by the significant bioactivities and therapeutic potential of 1,4-benzodioxan derivatives, we reported the asymmetric total synthesis of amovillosumins A (1) and B (2), two architecturally unique norlignans isolated from Amomum villosum. The target compounds were achieved in nine and seven steps, respectively, from commercially available materials, delivering exceptional overall yields (45-47 %) with excellent enantiopurity (91-95 % ee). The key synthesis strategies encompassed Williamson ether formation, stereocontrolled ketone reduction, and Ullmann coupling to establish the pivotal 1,4-dioxan scaffold.

Artemsieverlides A-M, diverse sesquiterpenoid dimers with antihepatic fibrosis activity isolated from Artemisia sieversiana based on molecular networking.

Artemsieverlides A-M (1-13), undescribed sesquiterpenoid dimers, were isolated from Artemisia sieversiana (Asteraceae) under the guidance of antihepatic fibrosis activity and molecular networking. Their structures were elucidated by spectral data (HRESIMS, UV, IR, 1D and 2D NMR), and ECD calculations. Of them, compounds 3, 7 and 12 were unambiguously confirmed by the single-crystal X-ray diffraction.

Antidiabetic diarylheptanoids from the leaves of Amomum tsao-ko and their inhibition mechanism against α-glucosidase.

Thirteen diarylheptanoids, including four undescribed ones (1-4), were isolated from the leaves of Amomum tsao-ko. Compounds 1 and 2 are two unusual diarylheptanoid-phenylpropanoid hybrids. Several of the isolates were tested for their biological activity in promoting GLP-1 secretion and inhibiting multiple type 2 diabetes-related enzymes.

Antidiabetic constituents of Kaempferiae rhizoma: Previously undescribed O-linked diarylheptanoid dimers promoting GLP-1 secretion via PKA-CREB pathway.

Glucagon-like peptide-1 (GLP-1) is a fascinating target for the treatment of diabetes to avoid hypoglycemia. Kaempferiae Rhizoma (KR), the dried rhizomes of Kaempferia galanga, is a famous pungent medicine used for activating Qi, warming interior, removing digestion and relieving pain in China. In order to characterize the antidiabetic effects of KR, 21 previously undescribed O-linked diarylheptanoid dimers, kaemgalangins A-A (1-4), B-B (5-17) and C-C (18-21), were isolated from the ethyl acetate fraction.

Apigenin alleviates inflammation as a natural IRAK4 inhibitor.

Background: Uncontrolled inflammation is a key factor in the development of many diseases, and targeting pivotal kinases involved in the inflammatory response, such as interleukin-1 receptor-associated kinase 4 (IRAK4), holds promise for the treatment of inflammatory conditions. Apigenin (Api) is a popular element in numerous plants, possessing anti-inflammatory properties. Many studies have shown that Api modulates NF-κB signaling and MAPK cascade to reduce inflammation, but the exact mechanisms by which Api regulates these pathways remain unclear.

New C-linked diarylheptanoid dimers as potential α-glucosidase inhibitors evidenced by biological, spectral and theoretical approaches.

Diabetes mellitus (DM) is a chronic metabolic disorder characterized by elevated blood glucose levels, generally due to defects of insulin action or secretion. Inhibition of α-glucosidase, an enzyme responsible for carbohydrate degradation, is a promising strategy for managing postprandial hyperglycemia in diabetic patients. In this study, two new C-linked diarylheptanoid dimers, kaemgalanganols A (1) and B (2), were isolated from K.

Artemordosins A-L, cadinane-monoterpene heterodimers and sesquiterpenoids with antihepatoma activity from Artemisia ordosica.

Two unprecedented sesquiterpene and monoterpene heterodimers and ten previously undescribed sesquiterpenoids, artemordosins A-L (1-12), as well as ten known sesquiterpenoids (13-22), were obtained from Artemisia ordosica. Their structures were elucidated based on comprehensive analyses of NMR, IR, HRESIMS, GIAO NMR calculations with DP4+ probability analysis, and ECD calculations. Notably, artemordosins A and B (1 and 2) were the first examples of cadinane-monoterpene dimers, and artemordosin A (1) was a cadinane-myrceane heterodimer with a 6/6/6/6 ring system formed by [4 + 2] cycloaddition, while artemordosin B (2) was a 4,5-seco-cadinane-artemisane dimer connected through a C-5-O-C-4' linkage.

Isospongian Diterpenoids from the Leaves of Amomum tsao-ko Promote GLP-1 Secretion via Ca/CaMKII and PKA Pathways and Inhibit DPP-4 Enzyme.

Three uncommon isospongian diterpenoids including a new one, 3-epi-kravanhin A (2), were isolated from the leaves of Amomum tsao-ko. Compounds 2 and 3 dose-dependently promoted GLP-1 secretion on STC-1 cells with promotion ratios of 109.7 % and 186.

New labdane diterpenoids from Alpinia galanga: A new type of GLP-1 secretagogues targeting the PKA-CREB and PI3K-Akt signaling axes.

Glucagon-like peptide-1 (GLP-1) secretagogues are fascinating pharmacotherapies to overcome the defects of GLP-1 analogs and dipeptidyl peptidase-4 (DPP-4) inhibitors in treating diabetes and obesity. To discover new GLP-1 secretagogues from natural sources, alpigalangols A-Q (1-17), 17 new labdane diterpenoids including four unusual nor-labdane and N-containing ones, were isolated from the fruits of Alpinia galanga. Most of the isolates showed GLP-1 promotive effects in NCl-H716 cells, of which compounds 3, 4, 12, and 14-17 were revealed with high promoting rates of 246.

Targeting adipocyte ESRRA promotes osteogenesis and vascular formation in adipocyte-rich bone marrow.

Excessive bone marrow adipocytes (BMAds) accumulation often occurs under diverse pathophysiological conditions associated with bone deterioration. Estrogen-related receptor α (ESRRA) is a key regulator responding to metabolic stress. Here, we show that adipocyte-specific ESRRA deficiency preserves osteogenesis and vascular formation in adipocyte-rich bone marrow upon estrogen deficiency or obesity.

Sesquiterpenoids from with GLP-1 Stimulative Effects through Ca/CaMKII and PKA Pathways and Multiple-Enzyme Inhibition.

Six new sesquiterpenoids (-), a pair of enantiomers ( and ), and six known ones (-) were isolated from the fruits of . The structures of the new compounds were elucidated by extensive spectroscopic data and ECD calculations. The stereochemistry of and was reported for the first time.

Two new guaiane-type sesquiterpenes from .

Two new guaiane-type sesquiterpenes, wenyujinolides A () and B (), were isolated from the ethanol extract of , together with 10 known compounds. Their structures were established by extensive spectroscopic methods (IR, ESIMS, HRESIMS, ECD, 1D and 2D NMR) and comparison of their NMR data with literatures. Compounds and were evaluated for the inhibition of NO production in LPS induced RAW 264.

Rubiginosin B selectively inhibits Treg cell differentiation and enhances anti-tumor immune responses by targeting calcineurin-NFAT signaling pathway.

Background: The accumulation of CD4Foxp3 regulatory T cells (Tregs) in the tumor microenvironment (TME) dampens anti-tumor immune responses and promotes tumor progression. Therefore, the elimination of Tregs has become a strategy to enhance the efficacy of tumor immunotherapy, although it is still a daunting challenge. Rhododendron brachypodum (R.

Diarylheptanoids with hypoglycemic potency from the rhizomes of Kaempferia galanga.

Five new diarylheptanoids, kaemgalangins A-E (1-5), and seven known ones were isolated from the rhizomes of Kaempferia galanga. The structures of new compounds were identified by spectroscopic analyses involving 1D and 2D NMR, HRESIMS, IR, UV, [α], ECD calculations, and chemical methods. All compounds were tested for their hypoglycemic effects against α-glucosidase, Gpa and PTP1B enzymes, and stimulative effects on GLP-1 secretion.

[Terpenoids from fruits of Amomum villosum and their hypoglycemic activity].

Eight terpenoids were isolated from the fruits of Amomum villosum by silica gel, Sephadex LH-20, Rp-C_(18), MCI GEL CHP20 P column chromatography, preparative TLC, and HPLC. Their structures were identified by HR-ESI-MS, ~1H and ~(13)C-NMR, IR, UV, [α]_D, and ECD spectroscopic data as kravanhin A 3-O-β-D-glucopyranoside(1), kravanhin B(2), 6-eudesmene-1β,4β-diol(3), oplodiol(4), vicodiol(5),(1R,2S,4R,7S)-vicodiol 9-O-β-D-glucopyranoside(6),(1R,2S,4S,5R)-angelicoidenol 2-O-β-D-glucopyranoside(7), and(1S,2S,4R,6S)-bornane-2,6-diol 2-O-β-D-glucopyranoside(8). Compound 1 was a new compound, and compounds 2-5 were isolated from A.

Synthesis and biological evaluation of paeoveitol D derivatives as new melatonin receptor agonists with antidepressant activities.

Our previous study demonstrated that paeoveitol D, a benzofuran compound isolated from , displayed activity on MT and MT receptors with agonistic ratios of 57.5% and 51.6% at a concentration of 1 mM.

Oligostilbenes from the seeds of Paeonia lactiflora as potent GLP-1 secretagogues targeting TGR5 receptor.

One unusual stilbene trimer-flavonoid hybrid, paeonilactiflobenoid (1), together with six known stilbenes (2-7) were isolated from the seeds of Paeonia lactiflora. The structure of 1 was elucidated with the aid of HRESIMS, 1D and 2D NMR, [α] spectroscopic data and ECD calculation. Compounds 2-7 showed stimulative effects on GLP-1 secretion with promoting rates of 79.

Distepharinamide, a novel dimeric proaporphine alkaloid from Diploclisia glaucescens, inhibits the differentiation and proliferative expansion of CD4Foxp3 regulatory T cells.

Background: CD4Foxp3 regulatory T cells (Tregs) represent the primary cellular mechanism of tumor immune evasion. Elimination of Treg activity by the pharmacological agent may enhance anti-tumor immune responses. However, Treg-eliminating agents, especially those with small molecules, are rarely reported.

Synthesis and biological evaluation of (+)-paeoveitol derivatives as novel antidepressants.

The antidepressant activity of (+) and (-)-paeoveitol was first evaluated using the forced swimming test (FST), and (+)-paeoveitol showed potential antidepressant activity by decreasing immobility time of mice (by approximately 26.4%) in the FST at a dose of 20 mg/kg. To explore the structure-activity relationships (SARs) and obtain more potent compounds, twenty derivatives of (+)-paeoveitol were synthesized and evaluated for their agonistic activities on melatonin type I (MT) and type II (MT) receptors.

Artemzhongdianolides A1-A21, antihepatic fibrosis guaiane-type sesquiterpenoid dimers from Artemisia zhongdianensis.

In the search for new antihepatic fibrosis candidates, it was observed that the EtOH extract of Artemisia zhongdianensis and EtOAc fraction had cytotoxicity against hepatic stellate cell line LX2 (HSC-LX2) with the inhibitory ratios of 85.7 % and 83.9 % at 400 μg/mL.