Diabetes Warriors from Heart Wood: Unveiling Dalbergin and Isoliquiritigenin from Dalbergia latifolia as Potential Antidiabetic Agents in-vitro and in-vivo.

Diabetes mellitus is a serious and complex metabolic disorder characterized by hyperglycemia. In recent years natural products has gained much more interest by researchers as alternative sources for diabetes treatment. Though many potential agents are identified so far but their clinical utility is limited because of their adverse effects. Therefore, there is a keen interest in discovering natural compounds to treat diabetes efficiently with less side effects. Dalbergia latifolia is well explored because of its diverse pharmacological activities including diabetes. Therefore, the present research work aimed to identify and isolate the potential antidiabetic agents from the heart wood of Dalbergia latifolia. We successfully extracted DGN and ISG from the heartwood and evaluated their antidiabetic potential both in-vivo and in-vitro. Alpha amylase activity inhibition of ISG and DGN was found to be 99.05 ± 8.54% (IC50 = 0.6025 µg/mL) and 84.68 ± 5.2% (IC50 = 0.0216 µg/mL) respectively. Glucose uptake assay revealed DGN (158%) promoted maximum uptake than ISG (77%) over control. In vivo anti diabetic activity was evaluated by inducing diabetes in SD rats with the help of HFD and STZ (35 mg/kg body weight). After the continuous administration of DGN (5 mg/kg, 10 mg/kg) and ISG (5 mg/kg, 10 mg/kg) for 14 days, we observed the reduction in the blood glucose levels, body weight, total cholesterol, low density lipoprotein, very low-density lipoprotein, blood urea, serum creatinine, serum glutamate oxaloacetic transaminase, serum glutamate pyruvate transaminase and alkaline phosphatase levels than vehicle group indicates the potency of ISG and DGN against diabetes.

Synthesis and appraisal of dalbergin-loaded PLGA nanoparticles modified with galactose against hepatocellular carcinoma: In-vitro, pharmacokinetic, and in-silico studies.

Hepatocellular carcinoma (HCC) is a common malignancy which affects a substantial number of individuals all over the globe. It is the third primary cause of death among persons with neoplasm and has the fifth largest mortality rate among men and the seventh highest mortality rate among women. Dalbergin (DL) is described to be effective in breast cancer via changing mRNA levels of apoptosis-related proteins. DL belongs to neoflavonoids, a drug category with low solubility and poor bioavailability. We created a synthetic version of this naturally occurring chemical, DL, and then analyzed it using 1H-NMR, 13C-NMR, and LC-MS. We also made PLGA nanoparticles and then coated them with galactose. The design of experiment software was used to optimize DL-loaded galactose-modified PLGA nanoparticles. The optimized DL-nanoformulations (DLF) and DL-modified nanoformulations (DLMF) were analyzed for particle size, polydispersity index, shape, and potential interactions. In-vitro experiments on liver cancer cell lines (HepG2) are used to validate the anti-proliferative efficacy of the modified DLMF. The in-vitro research on HepG2 cell lines also demonstrated cellular accumulation of DLF and DLMF by FITC level. The in-vitro result suggested that DLMF has high therapeutic effectiveness against HCC. In-vivo pharmacokinetics and bio-distribution experiments revealed that DLMF excelled pristine DL in terms of pharmacokinetic performance and targeted delivery, which is related to galactose's targeting activity on the asialoglycoprotein receptor (ASGPR) in hepatic cells. Additionally, we performed an in-silico study of DL on caspase 3 and 9 proteins, and the results were found to be -6.7 kcal/mol and -6.6 kcal/mol, respectively. Our in-silico analysis revealed that the DL had strong apoptotic properties against HCC.

Design and synthesis of dalbergin analogues and evaluation of anti-osteoporotic activity.

The chemical modifications of the hydroxyl group of dalbergin have been described via the introduction of cyclic amine, ester and amide groups. Among the twenty-three prepared novel analogues of dalbergin, compound 4d (EC50 2.3µM) showed significantly increased proliferation as assessed by alkaline phosphatase activity and mineralization in calvarial osteoblast cells in vitro. Compound 4d, at a dose of 1.0mg/kg body weight exhibited the significant osteoprotective effect. It showed a significant increase in osteogenic gene expression RunX2 (∼4fold), ALP (∼5fold), OCN (∼4fold) and COL1 (∼4fold) as compared to control group at the same dose in vivo assay.

Chemical constituents from rhizome of Smilax davidiana / 中草药

Objective: To study on the chemical constituents from the rhizome of Smilax davidiana. Methods: The compounds were separated and purified by sephadex LH-20 column chromatography and high performance liquid chromatography. Their structures were identified by spectroscopic analysis and comparison with literatures. Results: Twenty compounds were isolated and identified as aromadendrin7-O-β-D-glucopyranoside (1), dalbergin (2), 3,5,7,4′-tetrahydroxyflavanone-7-O-β-D-glucopyranoside (3), kaempferol-7-O-β-D-glucopyranoside (4), quercetin-7-O-β-D-glucopyranoside (5), quercetin-3-O-β-L-rhamnopyranoside (6), 4,6- dihydroxy-2-O-(β-D-glucopyranosyl)-acetophenone (7), 3,5-dihydroxy-4-O-(β-D-glucopyranosyl) acetophenone (8), 2,4,6- trihydroxy-acetophenone-4-O-β-D-glucopyranoside (9), 2,4,6-trihydroxylacetophenone-2,4-di-O-β-D-glucopyranoside (10), epicatechin (11), latifolin (12), 3′-O-(E-4-coumaroyl)-quinic acid (13), 5-O-caffeoylquinic acid butyl ester (14), 5,5′- dimethoxylariciresinol 4′-O-β-D-glucopyranoside (15), 1-cerotoylglycerol (16), cinchonain Ib (17), adenosine (18), resveratrol (19), and 3,4,5-trimethoxyphenyl-1-β-D-glucopyranoside (20). Conclusion: Compounds 4—9, and 12—16 are isolated from Smilax genus for the first time, and compounds 1—3, 17, and 18 are from S. davidiana for the first time.

Fast and long acting neoflavonoids dalbergin isolated from Dalbergia sissoo heartwood is osteoprotective in ovariectomized model of osteoporosis: Osteoprotective effect of Dalbergin.

OBJECTIVE: This study aims to evaluate the skeletal effects of dalbergin (DBN), isolated from Dalbergia sissoo heartwood, in ovariectomized (OVx) BALB/c mice, a postmenopausal osteoporosis model of bone loss. METHODS: Adult BALB/c mice were used and randomly assigned in to six groups with 6 animals (n=6) in each group: sham (surgery operated without ovariectomy) with vehicle, ovariectomy with vehicle, ovariectomy (OVx) with estradiol (E2 5.0µgkg-1day-1), or ovariectomy with dalbergin at three different doses of DBN (1.0, 5.0 and10mgkg-1day-1). Daily oral administration of the vehicle, estradiol, or DBN was started 8 weeks post-surgery and continued for 8 weeks. At the end of experiment, mice were sacrificed and assessed for trabecular bone structure of tibia, lumbar vertebra (L5) and alterations in biochemical and uterine parameters, pharmacokinetic profile and gene expression were monitored for each group. RESULTS: Treatment with DBN prevented trabecular bone loss in cancellous bone in the tibial metaphysis and lumbar vertebra region of the ovariectomized mice. Micro-CT data showed that mice treated with DBN at 1.0mgkg-1day-1 exhibited improved bone micro-architecture that was sustained with decreased expression of bone resorption markers like TRAP and RANK and caused an increase in osteogenic markers like RUNX2, BMP2 and OPG/RANKL ratio compared with OVx+vehicle treated mice. Moreover, DBN treatment induced no uterine estrogenicity and significantly lowered the osteocalcin amount in serum when compared with OVx+V group. DBN reached its maximum concentration (Cmax) 238.49±21.37ngml-1 in serum as early as 1h of administration. Overall, DBN (1.0mgkg-1day-1) treatment exhibited similar bone conserving effect against bone-loss as estradiol treatment. CONCLUSION: Daily oral administration of DBN for 8 weeks showed significant anabolic effects on bone micro-architectural parameters along with down regulation of bone resorptive markers without compromising safety at uterine level. Therefore, our study provides basis for DBN as a therapeutic candidate against postmenopausal osteoporosis.