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Ethnopharmacological Relevance: Dalbergia sissoo DC. (Indian rosewood or Sheesham) is a traditional medicinal plant, reported since time immemorial for its analgesic, anti-nociceptive, anti-inflammatory, and immuno-modulatory properties. D. sissoo DC (DS). is being used traditionally to cure joint inflammation and joint pain., Aim: To study the potential of DS leaves and its derived novel compound CAFG to treat the clinical symptoms of osteoarthritis (OA) and its underlying mechanism., Methods: The chemical profile of DS extract (DSE) with isoflavonoids and isoflvaonoid glycosides from the DS was established by UHPLC-PDA and UHPLC-MS/MS. Monosodium iodoacetate (MIA) was injected into the knee joint to develop the OA model in rats. DSE was given orally for 28 days daily at 250 and 500 mg.kg -1 day -1 . For in-vitro experiments, chondrocytes isolated from joint articular cartilage were negatively induced with interleukin-1β (IL-1β) and CAFG was given to the cells as a co-treatment., Results: Chondrocytes undergo apoptosis following inflammation and proteoglycan synthesis affected in MIA injected knees. DSE administration prevented these effects as assessed by H&E and Toluidine blue staining. Micro-CT analysis showed that subchondral bone loss was restored. DSE decreased elevated serum levels of cartilage-bone degradation (CTX-I, CTX-II, and COMP), inflammation markers IL-1β, and matrix-degrading MMP-3 and 13. The effects of IL-1β on gene expression of chondrocytes were reversed by CAFG treatment at 1 μM., Conclusion: Data showed that DSE protected joint cartilage and deterioration in subchondral bone in vivo while in in-vitro, its active ingredient CAFG prevented interleukin-1β induced effects and inhibited OA. This finding suggest that DSE and CAFG could be used as a possible therapeutic to treat osteoarthritis., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Extract of Ulmus wallichiana is being used as traditional medicine used for the treatment of fractured bones however the effect of its individual flavonols is not known. The present study was conducted to investigate the effect of its novel flavonol, (2S, 3S)-(+)-30, 40, 5, 7-tetrahydroxydihydroflavonol-6-C-b-d-glucopyranoside named as Ulmoside A (UA), on lipopolysaccharides (LPS) treated neurons. LPS treatment to neuronal cells caused significant cytotoxicity, reactive oxygen species generation, depletion in glutathione and mitochondrial impairment which were significantly inhibited with UA treatment. LPS treatment also caused significant translocation of cytochrome-c, decreased level of Bcl2, increased level of Bax and cleaved caspase-3 in neuronal cells reflecting the involvement of intrinsic apoptotic pathway in neuronal death which was attenuated with UA treatment. Since LPS is a well known pro-inflammatory agent it also offered the significant increase in proinflammatory cytokines (tumor necrosis factors-α & interleukin 1-beta) however, UA treatment did not exhibit significant inhibition against LPS induced inflammatory response. LPS also caused the augmented level of inducible nitric oxide synthase (iNOS) which was also not inhibited with co treatment of UA. We have also observed the significant DNA fragmentation and augmented level of cleaved Poly (ADP-Ribose) polymerase 1 after LPS treatment which was significantly reverted with UA treatment. Findings suggested that UA acts through mitochondria and exhibited its anti-oxidative and anti-apoptotic activities in neuronal cells while no significant anti-inflammatory activity and effect on iNOS were observed., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Phytochemical investigation of Cissus quadrangularis stems led to the isolation of one new phenolic glycoside (1) and two new lignan glycosides (7 & 8) along with twelve known compounds (2-6 & 9-15). Their chemical structures were determined on the basis of extensive spectroscopic analysis using 1D, 2D NMR, and mass spectrometric analysis. Among the known compounds, 4-6, 9 and 12 were isolated for the first time from the genus Cissus whereas compounds 10, 11 and 13 for the first time from this plant.

Objective: Atherogenic diet (AD) and high fat diet (HFD) cause deleterious effect on bone micro-architecture and this phenomenon prompts aortic calcification. This study aims to show the effects of Caviunin β-d-glucopyranoside (CAFG), against bone loss and its associated aortic calcification in presence of AD and HFD challenged diets., Methods: Five groups of C57BL/6 male mice with 8 animals in each group, comprising of chow, AD, HFD, AD+CAFG and HFD+CAFG were fed with respective diets for 16 weeks. At the end of the treatment period, preventive effects of CAFG on bone tissue were analyzed by assessing the osteogenic potential of bone marrow cells, bone micro-architecture, ability of new bone formation and histomorphometry studies. Aortic calcification was assessed by transcription and translation analysis of osteogenic key markers in aortic tissue and assessment of aortic endothelial function. Plasma lipid profiling was done to assess the effects of diets as its role in both bone loss and aortic calcification., Results: Bone marrow stromal cell (BMSC's) dynamics showed that AD and HFD decreased osteoblast number that led to bone loss, deterioration in bone micro-architecture with up-regulated bone resorptive genes that lead to increase in aortic calcification. CAFG treatment rescued the bone health by modulating BMSC's towards osteogenic lineage. It increased the osteogenic gene expression with simultaneous decrease in osteoclastic genes thus stabilized the receptor activator of nuclear factor-kappa-B ligand/osteoprotegerin ratio that eventually reduced the amount of calcification in aorta. Biochemical studies showed that CAFG reduced the TC, TG and LDL-C content with no marked changes in HDL-C. Moreover, CAFG decreased the osteogenic key markers in the aortic tissue and enhanced endothelial function., Conclusion: Overall, this study indicates that CAFG protected against physiologically challenged diet induced bone loss with associated vascular calcification in mice. Moreover, data revealed that atherogenic diet is more detrimental as compared to the excess fatty acid diet to the bone and aorta., (Copyright © 2017. Published by Elsevier Masson SAS.)

Phytochemical investigation of the n-butanol fraction of Evolvulus alsinoides (Linn.) led to the isolation of three new phenolic glycosides, evolvosides C, D and E (1-3) along with six known compounds (4-9). The structures of the compounds were elucidated on the basis of spectroscopic analysis, viz. 1D and 2D NMR experiments, chemical study, and comparison with literature data. Evolvoside C (1) was characterized as kaempferol 4'-O-β-D-glucopyranosyl-(1→2)-α-L-rhamnopyranosyl-(1→6)-β-D-glucopyranoside, whereas evolvosides D and E (2-3) were found to be mono and di-O-methyl derivatives of 1. The new compounds (1-3) represent rare triglycoside derivatives of flavonol at C-4'. The isolated compounds (1-6) were screened for acute stress-induced biochemical changes in male Sprague-Dawley rats at a dose of 40 mg/kg body weight. Compounds 1 and 2 displayed anti-stress effects by normalizing hyperglycemia, plasma corticosterone, plasma creatine kinase, and adrenal hypertrophy. Compounds 3 and 6 were also found to be effective in normalizing most of these stress parameters, whereas compounds 4 and 5 were ineffective in normalizing most of these effects., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

(2S,3S)-Aromadendrin-6-C-β-d-glucopyranoside (AG) is a novel flavonol isolated from the extract of Ulmus wallichiana (Himalayan Elm). Extract of U. wallichiana is used as a traditional medicine for rapid fracture repair in India. We characterized the mechanism of action of AG in mouse bone cells by investigating its effect on the precursors of osteoblasts, osteoclasts and adipocytes. At nanomolar concentrations, AG increased differentiation of preosteoblasts obtained from neonatal mouse calvaria. The gene expression of osteogenic markers, including runt-related transcription factor 2 (Runx-2), bone morphogenetic protein-2 (BMP-2), type I collagen and osteocalcin were elevated in the preosteoblasts. The extracellular matrix mineralization was higher in preosteoblast and bone marrow cells when AG was present in the medium. Furthermore, AG protected the differentiated osteoblasts from serum deprivation-induced apoptosis, and increased the expression of the anti-osteoclastogenic cytokine, osteoprotegerin. It inhibited osteoclast differentiation of bone marrow precursor cells to osteoclasts in the presence of receptor activator of nuclear factor kappa-B ligand (RANKL) and monocyte/macrophage-colony stimulating factor (M-CSF). Additionally, in 3T3-L1 preadipocytes, AG decreased the expression of genes involved in adipogenesis, including peroxisome proliferator-activated receptor gamma (PPARγ), sterol regulatory element binding protein (SREBP) and CCAAT/enhancer-binding protein alpha (CEBP/α), and induced apoptosis of differentiated adipocytes. Induction of adipogenic differentiation was also inhibited in the presence of AG. AG exhibited no estrogenic/antiestrogenic effect. Together, our data show that AG has potent osteogenic, anti-osteoclastogenic and anti-adipogenic effects, which may translate to a better skeletal outcome in postmenopausal osteoporosis., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Phytochemical investigation of Dodecadenia grandiflora leaves led to the isolation and identification of three phenolic glycosides, designated 1-[(4'-O-(E)-p-coumaroyl)-beta-D-glucopyranosyl]-oxy-2-phenol (1), 1-[(6'-O-(E)-p-coumaroyl)-beta-D-glucopyranosyl]-oxy-2-phenol (2) and 1-[O-beta-D-glucopyranosyl(1-->2)-beta-D-glucopyranosyl]-oxy-2-phenol (3), along with nine known compounds. Compounds 1, 2, 5 and 9 exhibited significant glucose-6-phosphatase inhibitory activity (63.7, 66.9, 82.9 and 85.4%) with IC(50) values of 88.5, 81.0, 51 and 50 microM respectively. On the basis of biological results, a structure-activity relationship has been discussed., (Copyright (c) 2010 Elsevier B.V. All rights reserved.)

Oxidative damage is an established outcome of chronic stress. Thus, the present study was designed to investigate the modulatory role of ethanolic extract of Evolvulus alsinoides (EA) in terms of oxidative alterations at peripheral and central level in rats subjected to chronic unpredictable stress (CUS). CUS exposure for 7 days reduced Cu, Zn superoxide dismutase and catalase activity with increase in glutathione peroxidase activity and lipid peroxidation, while decrease in reduced glutathione level in blood plasma, frontal cortex and hippocampus regions of brain. Oral administration of EA extract at 200mg/kg p.o. normalized these stress induced oxidative alterations with an efficacy similar to that of melatonin. Further, EA extract was taken up for detailed chemical investigation. Two new flavonol-4'-glycoside, kaempferol 4'-O-beta-D-glucopyranosyl-(1-->2)-beta-D-glucopyranoside (3) and kaempferol 4'-O-alpha-L-rhamnopyranosyl-(1-->6)-beta-D-glucopyranoside (5) were isolated, along with eight known compounds (1, 2, 4 and 6-10). The structures of new compounds were established by detailed spectroscopic studies, while known compounds were characterized by direct comparison of their reported NMR data. All these compounds were evaluated for their in vitro antioxidant activity. Compounds 3, 5, 9 and 10 at 100 and 200 microg/ml showed significant in vitro antioxidant activity. Therefore, EA may hold great potential in preventing clinical deterioration in stress induced oxidative load and related disorders., ((c) 2009 Elsevier B.V. All rights reserved.)

Objective: The aim of this study was to determine the skeletal effect of 6-C-beta-d-glucopyranosyl-(2S,3S)-(+)-3',4',5,7-tetrahydroxyflavanone (GTDF)/Ulmoside A, a new compound isolated from the extract of Ulmus wallichiana in a rat model of postmenopausal bone loss., Methods: GTDF (1.0 and 5.0 mg kg d) was given orally to ovariectomized (OVx) rats (180-200 g) for 12 weeks. Sham operated + vehicle, ovariectomy + 17beta-estradiol (2.5 microg kg d), and ovariectomy + vehicle groups served as various controls. Bone mineral density (BMD), trabecular microarchitecture, bone biomechanical strength, levels of bone turnover/resorption markers, uterotropic effect, and plasma pharmacokinetics were studied. One-way analysis of variance was used to test significance of effects., Results: OVx rats treated with both doses of GTDF exhibited significantly higher BMD in the trabecular (distal femur, proximal tibia, and vertebrae) and cortical (femur shaft) regions compared with the ovariectomy + vehicle group. Micro-CT demonstrated that OVx rats treated with 5.0 mg kg day of GTDF had better bone microarchitectural parameters compared with the ovariectomy + vehicle group. Serum osteocalcin and urinary C-terminal teleopeptide of Type I collagen levels in OVx rats treated with GTDF (at both doses) were significantly lower than those in the ovariectomy + vehicle group. At neither of the two doses did GTDF exhibit uterine estrogenicity. A pharmacokinetic study revealed that GTDF achieved maximum plasma concentration (40.67 ng mL) at approximately 1 hour, indicating its slow absorption. Its absolute bioavailability was found to be 1.04% with a plasma elimination half-life of approximately 5 hours., Conclusions: GTDF, a novel compound isolated from U wallichiana extract, improves bone biomechanical quality through positive modifications of BMD and trabecular microarchitecture without a hyperplastic effect on the uterus.

Objective: This study aimed to determine the skeletal effects of total ethanolic extract (TEE) and its butanolic fraction (BF) from the stem-bark of Ulmus wallichiana, which is rich in C-glycosylated flavonoids, in growing rats (for peak bone [PB] achievement) and in ovariectomized (OVx) rats (for menopausal bone loss)., Methods: TEE (750 mg kg(-1) d(-1)) and BF (50 mg kg(-1) d(-1)) were given orally for 10 weeks to weaning female Sprague-Dawley rats and for 12 weeks to adult OVx rats of the same strain, respectively. In studies with OVx rats, sham operated + vehicle, OVx + 17beta-estradiol, and OVx + vehicle groups served as various controls. Bone mineral density (BMD), biomechanical strength, bone histology, formations of osteoprogenitor cells, osteoid formation, and bone turnover/resorption markers were studied. Bioactive marker compounds in TEE and BF were analyzed by high-performance liquid chromatography. One-way analysis of variance was used to test significance of effects., Results: In growing rats, both TEE and BF increased BMD, bone strength, and bone formation rate, suggesting higher PB achievement. OVx rats treated with either TEE or BF exhibited increased BMD at various anatomical positions and improved bone strength and trabecular architecture compared with the OVx + vehicle group. Serum osteocalcin and urinary type 1 collagen degradation product levels in OVx rats treated with either TEE or BF were significantly lower than those of the OVx + vehicle group. Neither TEE nor BF exhibited uterine estrogenicity. Analysis of marker compounds revealed significant enrichment of two bioactive markers in BF over TEE., Conclusions: Derived from U wallichiana, BF at much a lower dose than TEE was effective in PB achievement and prevention of OVx-induced bone loss.

Chemical investigation of Ulmus wallichiana stem bark resulted in isolation and identification of three new compounds (2S,3S)-(+)-3',4',5,7-tetrahydroxydihydroflavonol-6-C-beta-D-glucopyranoside (1), (2S,3S)-(+)-4',5,7-trihydroxydihydroflavonol-6-C-beta-D-glucopyranoside (3) and 3-C-beta-D-glucopyranoside-2,4,6-trihydroxymethylbenzoate (8), together with five known flavonoid-6-C-glucosides (2, 4-7). Their structures were elucidated using 1D and 2D NMR spectroscopic analysis. The absolute stereochemistry in compounds 1 and 3 were established with the help of CD data analysis and comparison with the literature data analysis. All the isolated compounds (1-8) were assessed for promoting the osteoblast differentiation using primary culture of rat osteoblast as an in vitro system. Compounds 1-3 and 5 significantly increased osteoblast differentiation as assessed by alkaline phosphatase activity.

From the ethanolic extract of stem bark of D. angustifolia three new compounds, a coumaroyl triterpene lactone, diospyrosooleanolide (1), a phenolic glycoside, diospyrososide (2) and a naphthalene glycoside, diospyrosonaphthoside (3) were isolated along with five known compounds (4-8). The structures of these compounds were established on the basis of spectroscopic and chemical evidences.

Pongamia pinnata fruits afforded three new furanoflavonoid glucosides, pongamosides A-C (1-3), and a new flavonol glucoside, pongamoside D (4). The structures of these compounds were established on the basis of spectroscopic studies. This is the first time that furanoflavone glucosides have been found as naturally occurring compounds.

The Dalbergia sissoo leaves traditionally have medicinal values and are well known for current research on osteoporosis and bone health. The present research aims to develop and validate a simple, sensitive, and comprehensive analytical method to standardize Dalbergia sissoo leaves. An ultra‐high performance liquid chromatography method was developed for seven isoflavone glycosides, and isoflavone's identification, including bioactive caviunin and biochanin‐A based glycosides with genistein, pratensein, biochanin‐A, and biochanin‐A‐7‐O‐glucoside for simultaneous quantification in Dalbergia sissoo leaves. Also, a novel high‐performance thin‐layer chromatography‐based method has been developed for isoflavone glycosides as a visual quality control tool for Dalbergia sissoo. Further, seven isoflavonoids were also characterized using mass spectrometry in sample matrices. A qualitative high‐performance thin‐layer chromatography‐based method was found helpful in identifying four major isoflavone glycosides in leaves. The performance of the method and the validation data showed the ultra‐high performance liquid chromatography method was precise (relative standard deviation < 5.0%), accurate (recoveries 80%–110%), robust (relative standard deviation < 5.0%), and linear (r2 > 0.99) for quantification. This well‐separated novel and rapid determination of Dalbergia sissoo compounds in leaves will be helpful in the standardization of the quality assessment tool for Dalbergia sissoo. [ABSTRACT FROM AUTHOR]

Phytochemical investigation of Bacopa procumbens afforded two new phenolic glycosides 1 and 2 , for the first time, along with 12 known compounds 3 - 14 . Structures of these compounds were established based on spectral and chemical evidences. [ABSTRACT FROM AUTHOR]

Four new clerodane furano diterpene glucosides (amritosides A, B, C and D) were isolated as their acetates from Tinospora cordifolia stems. The structures of these compounds were established on the basis of spectroscopic studies. [Copyright &y& Elsevier]

Abstract: Various phenolic C-glycosides were evaluated for their in vitro and in vivo antihyperglycemic activity employing glucose uptake by rat muscle cell lines (L-6) and low dosed-streptozotocin-induced diabetic rats, respectively. Some of phenolic C-glycosides were isolated from Pterocarpus marsupium and Ulmus wallichiana and other were synthesized by unprotected sugar and phloroacetophenone using Sc(OTf)3 in aqueous ethanol. Eight among tested compounds showed significant lowering of blood glucose level on low dosed-streptozotocin-induced diabetic rats. The compound 24 lowered the blood glucose levels by 34.9% and 33.6% during 0–5h and 0–24h, respectively, at the dose of 25mg/kg body weight which is comparable to standard antidiabetic drug metformin. [Copyright &y& Elsevier]

Two new phenolic glycosides (1, 2), along with fourteen known compounds (3–16) have been isolated from the fruit of Cupressus sempervirens. The structures of these compounds were determined by spectroscopic analysis and were evaluated for their inhibitory activity against glycogen phosphorylase and glucose-6-phosphatase enzymes. Compounds 14 showed a moderate inhibition against glucose-6-phosphatase and 15 against glycogen phosphorylase enzymes. [Copyright &y& Elsevier]

Abstract: Bioactivity-guided separation of an antihyperglycemic extract from the leaves of Dodecadenia grandiflora afforded two phenylpropanoyl esters of catechol glycosides (1 and 4) and two lignane bis(catecol glycoside)esters (2 and 3). Their structures were established on the basis of extensive spectroscopic analysis (1D and 2D-NMR, MS). Compounds 2 and 3 are believed to be derived from dimerization via the two phenylpropanoid units of 1. Compounds 1–4 showed significant antihyperglycemic activity in streptozotocin-induced (STZ) diabetic rats, which is comparable to the standard drug metformin. Our results provide support to explain the use of D. grandiflora as antihyperglycemic agent by the traditional medical practitioners. [Copyright &y& Elsevier]