Green and proficient process for industrial-scale preparation of Gymnema sylvestre standardized-extract enriched with Gymnemic acids through polymer-matrix-adsorption to reduce hyperglycemia

Deepak Kumar,Vipin Kumar Singh,Narayan Prasad Yadav,Sudeep Tandon,Karuna Shanker,Chandan Singh Chanotiya,Narendra Kumar,Puja Khare,Anirban Pal,Debabrata Chanda,Dharmendra Saikia,Yusuf Hussain,Abha Mee 한국공업화학회 2022 Journal of Industrial and Engineering Chemistry Vol.116 No.-

Gymnema sylvestre is an important medicinal plant, but a method for preparing standardized extractenriched with biomarkers is not available. The practiced crude hydro-alcoholic extracts of G. sylvestrecontained a few percentage of gymnemic acids (GAs). The enrichment of GAs in preprared extracts isessential from a pharmacology point of view. Presently, a scale-up process has been developed forpreparing G. sylvestre standardized extract (Gym-EEXT). Crude extract (Gym-Crude) was prepared in10-kg batches to obtain a yield of 268.1 mg/g, but GAs was merely 9 mg/g (GA-IV 6.7 mg/g, and GAXVII2.3 mg/g) in 30 % ethanol–water solvent at 50 C in 5 h. Further, Gym-Crude was processed throughpolymer-matrix-adsorption techniques for getting Gym-EEXT (150.9 mg/g) with improved percentage ofGAs (>10 %) comprised of deacylgymnemic acid (DGA: 8.9 mg/g), gymnemagenin (2.3 mg/g), GA-IV(78.6 mg/g), and GA-XVII (10.2 mg/g). For safety aspects, the pesticide residues, solvent residues, heavymetal, aflatoxins, and mutagenicity in Gym-EEXT were below the detection limits. Hence, Gym-EEXT wasenriched with GAs, and fully safe with compliance according to USP-561. An insignificant effect of Gym-EEXT on vitals of experimental mice was observed in acute and sub-acute oral-toxicityexperiments. Gym-EEXT significantly improved the blood glucose metabolism, and hence, it potentiallyreduces hyperglycaemia. Unique chromatographic protocols were developed for the isolation of biomarkerson a 1-kg scale from Gym-Crude with yield of gymnemagenin (5.5 %), and DGA (4.6 %). Finally, a novel,scientifically validated, and the scale-up process has been developed for the preparation of Gym-EEXTalong with an exclusive protocol for isolating its biomarkers.

Molecular docking, QSAR and ADMET studies of withanolide analogs against breast cancer

Yadav, Dharmendra K,Kumar, Surendra,Saloni,Singh, Harpreet,Kim, Mi-hyun,Sharma, Praveen,Misra, Sanjeev,Khan, Feroz Dove Medical Press 2017 Drug design, development and therapy Vol.11 No.-

<P>Withanolides are a group of pharmacologically active compounds present in most prodigal amounts in roots and leaves of <I>Withania somnifera</I> (Indian ginseng), one of the most important medicinal plants of Indian traditional practice of medicine. Withanolides are steroidal lactones (highly oxygenated C-28 phytochemicals) and have been reported to exhibit immunomodulatory, anticancer and other activities. In the present study, a quantitative structure activity relationship (QSAR) model was developed by a forward stepwise multiple linear regression method to predict the activity of withanolide analogs against human breast cancer. The most effective QSAR model for anticancer activity against the SK-Br-3 cell showed the best correlation with activity (<I>r</I><SUP>2</SUP>=0.93 and rCV<SUP>2</SUP> =0.90). Similarly, cross-validation regression coefficient (rCV<SUP>2</SUP>=0.85) of the best QSAR model against the MCF7/BUS cells showed a high correlation (<I>r</I><SUP>2</SUP>=0.91). In particular, compounds CID_73621, CID_435144, CID_301751 and CID_3372729 have a marked antiproliferative activity against the MCF7/BUS cells, while 2,3-dihydrowithaferin A-3-beta-<I>O</I>-sulfate, withanolide 5, withanolide A, withaferin A, CID_10413139, CID_11294368, CID_53477765, CID_135887, CID_301751 and CID_3372729 have a high activity against the Sk-Br-3 cells compared to standard drugs 5-fluorouracil (5-FU) and camptothecin. Molecular docking was performed to study the binding conformations and different bonding behaviors, in order to reveal the plausible mechanism of action behind higher accumulation of active withanolide analogs with β-tubulin. The results of the present study may help in the designing of lead compound with improved activity.</P>

Electroosmotic flow of biorheological micropolar fluids through microfluidic channels

Mithilesh Kumar Chaube,Ashu Yadav,Dharmendra Tripathi,O. Anwar Bég 한국유변학회 2018 Korea-Australia rheology journal Vol.30 No.2

An analytical analysis is presented in this work to assess the influence of micropolar nature of fluids in fully developed flow induced by electrokinetically driven peristaltic pumping through a parallel plate microchannel. The walls of the channel are assumed as sinusoidal wavy to analyze the peristaltic flow nature. We consider that the wavelength of the wall motion is much larger as compared to the channel width to validate the lubrication theory. To simplify the Poisson Boltzmann equation, we also use the Debye-Hückel linearization. We consider governing equation for micropolar fluid in absence of body force and couple effects however external electric field is employed. The solutions for axial velocity, spin velocity, flow rate, pressure rise, and stream functions subjected to given physical boundary conditions are computed. The effects of pertinent parameters like Debye length and Helmholtz-Smoluchowski velocity which characterize the EDL phenomenon and external electric field, coupling number and micropolar parameter which characterize the micropolar fluid behavior, on peristaltic pumping are discussed through the illustrations. The results show that peristaltic pumping may alter by applying external electric fields. This model can be used to design and engineer the peristalsis-lab-on-chip and micro peristaltic syringe pumps for biomedical applications.

Evaluation of early versus delayed laparoscopic cholecystectomy in acute calculous cholecystitis: a prospective, randomized study

Gaurav Gupta,Ajay Shahbaj,Dharmendra Kumar Pipal,Pawan Saini,Vijay Verma,Sangeeta Gupt,Vibha Rani,Seema Yadav 대한내시경로봇외과학회 2022 Journal of Minimally Invasive Surgery Vol.25 No.4

Purpose: Uncertainty exists about whether early laparoscopic cholecystectomy (LC) is an appropriate surgical treatment for acute calculous cholecystitis. This study aimed to compare early vs. late LC for acute calculous cholecystitis regarding intraoperative difficulty and postoperative outcomes. Methods: This was a prospective randomized study carried out between December 2015 and June 2017; 60 patients with acute calculous cholecystitis were divided into two groups (early and delayed groups), each comprising 30 patients. Thirty patients treated with LC within 3 to 5 days of arrival at the hospital were assigned to the early group. The other 30 patients were placed in the delayed group, first treated conservatively, and followed by LC 3 to 6 weeks later. Results: The conversion rates in both groups were 6.7% and 0%, respectively (p = 0.143). The operating time was 56.67 ± 11.70 minutes in the early group and 75.67 ± 20.52 minutes in the delayed group (p = 0.001), and both groups observed equal levels of postoperative complications. Early LC patients, on the other hand, required much fewer postoperative hospital stay (3.40 ± 1.99 vs. 6.27 ± 2.90 days, p = 0.006). Conclusion: Considering shorter operative time and hospital stay without significant increase of open conversion rates, early LC might have benefits over late LC.

Biomedical features and therapeutic potential of rosmarinic acid

Saba Noor,Taj Mohammad,Malik Abdul Rub,Ali Raza,Naved Azum,Dharmendra Kumar Yadav,Md Imtaiyaz Hassan,Abdullah M. Asiri 대한약학회 2022 Archives of Pharmacal Research Vol.45 No.4

For decades, the use of secondary metabolitesof various herbs has been an attractive strategy in combatinghuman diseases. Rosmarinic acid (RA) is a bioactivephenolic compound commonly found in plants of Lamiaceaeand Boraginaceae families. RA is biosynthesizedusing amino acids tyrosine and phenylalanine via enzymecatalyzedreactions. However, the chemical synthesis of RAinvolves an esterifi cation reaction between caff eic acid and3,4-dihydroxy phenyl lactic acid contributing two phenolicrings to the structure of RA. Several studies have ascertainedmultiple therapeutic benefi ts of RA in various diseases,including cancer, diabetes, infl ammatory disorders, neurodegenerativedisorders, and liver diseases. Many previousscientifi c papers indicate that RA can be used as an antiplasmodic,anti-viral and anti-bacterial drug. In addition,due to its high anti-oxidant capacity, this natural polyphenolhas recently gained attention for its possible applicationas a nutraceutical compound in the food industry. Here we provide state-of-the-art, fl exible therapeutic potential andbiomedical features of RA, its implications and multipleuses. Along with various valuable applications in safeguardinghuman health, this review further summarizes thetherapeutic advantages of RA in various human diseases,including cancer, diabetes, neurodegenerative diseases. Furthermore,the challenges associated with the clinical applicabilityof RA have also been discussed.