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Determination of solubility, stability and degradation kinetics of morin hydrate in physiological solutions.

ABSTRACT: Natural drugs have emerged as potential alternatives to synthetic drugs to avoid their toxic effects. Morin hydrate (MH) is a natural therapeutic agent, obtained from Maclura pomifera, Maclura tinctoria and Psidium guajava. Solubility and degradation kinetics of morin hydrate in different physiological media, namely, 0.1 N HCl (pH 1.2), sodium acetate buffer (pH 5.0), water (pH 7.0), phosphate buffer saline (pH 7.4) and tris base (pH 9.0), were investigated via classical spectroscopic methods. Stability studies of MH were performed to determine the effect of different pH media, temperature (room and freeze) and light on the degradation kinetics. Solubility and stability of MH varied significantly in different biological media and storage conditions. Solubility of MH was pH-dependent and increased with the increase in pH. Degradation kinetics and regression values (r ²) values were calculated from the linear fitted models of zero, first and second order kinetics.

SUBMITTER: Jangid AK

PROVIDER: S-EPMC9084450 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Determination of solubility, stability and degradation kinetics of morin hydrate in physiological solutions.

Jangid Ashok Kumar AK Pooja Deep D Kulhari Hitesh H Kulhari Hitesh H

RSC advances 20180814 50

Natural drugs have emerged as potential alternatives to synthetic drugs to avoid their toxic effects. Morin hydrate (MH) is a natural therapeutic agent, obtained from Maclura pomifera, Maclura tinctoria and Psidium guajava. Solubility and degradation kinetics of morin hydrate in different physiological media, namely, 0.1 N HCl (pH 1.2), sodium acetate buffer (pH 5.0), water (pH 7.0), phosphate buffer saline (pH 7.4) and tris base (pH 9.0), were investigated via classi ...[more]

PMID: 35548393

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Project description:Chemoresistance is a major obstacle that limits the benefits of cisplatin-based chemotherapy in various cancers, including hepatocellular carcinoma. De-regulation of the poly(ADP-ribose) polymerase 1 (PARP1)/high-mobility group box 1 (HMGB1) signaling pathway has been proposed as an important mechanism involved in cisplatin-resistance. In this study, we investigated therapeutic potential of a natural flavonoid Morin hydrate against cisplatin-induced toxicity using the HepG2DR multi-drug resistant cell line, which is derived from the HepG2 human hepatocellular carcinoma cell line. HepG2DR cells were exposed to cisplatin and Morin hydrate alone or together after which autophagy and apoptotic signaling pathways were monitored by fluorometric assay and Western blot analysis. Xenograft mouse models were performed to confirm the in vitro effect of Morin hydrate. PARP1 was hyper activated in cisplatin-resistant HepG2DR cells. Cisplatin-induced PARP1 activation resulted in chemoresistance via increased autophagy. The cisplatin/Morin hydrate combination was effective in the reversal of the HepG2DR cell resistance via suppression of PARP1-mediated autophagy by regulating the HMGB1 and microtubule-associated protein 1A/1B light chain 3B (LC3) I/II. Moreover, PARP1 inhibition by 4-amino-1,8-naphthalimide or autophagy inhibition by a knockdown of the autophagy-related 5 (Atg5) gene resulted in sensitizing the HepG2DR cells to cisplatin (CP) through activation of the c-Jun N-terminal kinase (JNK) pathway. In a mouse xenograft model, the treatment of cisplatin with Morin hydrate reversed the increased expression of PARP and HMGB1 and significantly suppressed tumor growth. These findings indicate dysregulated expression of PARP1 confers cisplatin-resistance via autophagy activation in HepG2DR cells. Morin hydrate inhibits cisplatin-mediated autophagy induction, resulting in increased susceptibility of HepG2DR cells to cisplatin cytotoxicity. The combination of Morin hydrate with cisplatin may be a promising therapeutic strategy to enhance the efficacy of conventional chemotherapeutic drugs.

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Determination of solubility, stability and degradation kinetics of morin hydrate in physiological solutions.

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Determination of solubility, stability and degradation kinetics of morin hydrate in physiological solutions.

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