OBJECTIVESTo elucidate the association between the anticancer activities of piperlongumine (PL) and its potential target, transient receptor potential melastatin 7 channel (TRPM7), in oral squamous cell carcinoma (OSCC).METHODSThe expression levels and electrical characteristics of TRPM7 as well as cell viability in response to various PL treatments were investigated in the OSCC cell line Cal27.RESULTSPL treatment resulted in a concentration- and time-dependent reduction in TRPM7 mRNA and protein expression in Cal27 cells. Furthermore, PL treatment inhibited TRPM7-like rectifying currents in Cal27 cells; however, this inhibition was less effective than that of the TRPM7 antagonist waixenicin A. Rapid perfusion and washout experiments revealed an immediate inhibitory effect of PL on TRPM7-like currents. The antagonistic effect of PL occurred within 1 min and was not completely reversed following washout. Notably, the extracellular Ca²⁺ concentration still influenced PL-induced changes in the TRPM7-like current, indicating that PL can directly but gently antagonize the TRPM7 channel. Functional changes in TRPM7 correlated with the observed antiproliferative and cytotoxic effects of PL in Cal27 cells.CONCLUSIONSThese findings suggest that PL exhibits potent inhibitory effects on TRPM7 and exerts its anti-cancer effects by downregulating TRPM7 expression and antagonizing channel currents.

01 May 2024·Journal of Ethnopharmacology

Phytochemical profiling and nephroprotective potential of ethanolic leaf extract of Polyalthia longifolia against cisplatin-induced oxidative stress in rat model

Article

Author: Kumar, Ramesh ; Shrivastava, Sadhana ; Bisht, Divya ; Shakya, Arvind Kumar ; Prakash, Deena

ETHNOPHARMACOLOGICAL RELEVANCEKidney problems are becoming more common globally and are considered a major health issue in the modern world with high mortality rate. Polyalthia longifolia (Sonn.) Thwaites is a tropical ethnomedicinal plant used to treat various diseases like diabetes, hypertension and urinary disorders and possess antioxidant and anti-inflammatory properties.AIM OF THE STUDYThis study aimed to investigate the phytochemical composition of 70% ethanolic leaf extract of Polyalthia longifolia (Sonn.) Thwaites (PL) and evaluates its nephroprotective effects against cisplatin-induced nephrotoxicity in Wistar rats.MATERIALS AND METHODSThe leaves of PL were extracted with 70% ethanol and performed the phytochemical profiling using Liquid Chromatography-Mass Spectrometry (LC-MS). The nephroprotective effect of PL leaf extract was evaluated at three doses (150, 300 and 600 mg/kg, p.o.) for 14 days against cisplatin toxicity (16 mg/kg, i.p., once) in male Wistar rats. Body and kidney weight indices, kidney function markers and lipid profile markers in serum, and oxidative stress markers in kidney tissue were performed along with the histopathological analysis of kidney.RESULTSThe LC-MS chromatograph confirmed the presence of various phytocompounds include N-Methylhernagine (aporphine alkaloid), 4-Acetamidobutanoic acid (gamma amino acid) and choline, etc. in the PL leaf extract. Exposure of cisplatin (16 mg/kg, i.p., once only) to the animals significantly elevated the levels of kidney functional markers (i.e. serum urea, uric acid, creatinine) and the lipid markers (triglyceride and total cholesterol) in blood circulation with depletion of serum albumin which were reversed by the therapy of PL leaf extract (150, 300 and 600 mg/kg) in dose-dependent manner. The altered level of body and kidney weight in cisplatin treated group was also restored by the therapy. PL leaf extract effectively improved the antioxidant defense system of kidney at all doses by restoring the levels of tissue glutathione, superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase with the dose-dependent reduction of lipid peroxidation against cisplatin-induced renal oxidative stress. The histopathological observations also showed the significant recovery in cellular morphology after PL treatment when compared to the cisplatin toxicity group. The highest dose 600 mg/kg of PL leaf extract showed more pronounced renal recovery (p < 0.001) followed by other two doses, which was similar to the silymarin treatment group (a reference drug) against nephrotoxicity.CONCLUSIONThe results of this study revealed the nephroprotective effects of PL leaves against cisplatin-induced nephrotoxicity by reversing the level of biochemical markers and mitigating oxidative stress as well as improving the architecture of renal tissues. This renal protection by PL might be due to the synergistic effect of its phytoconstituents and antioxidant efficacy.

01 May 2024·Science of The Total Environment

Enhancing phytoremediation of cadmium and arsenic in alkaline soil by Miscanthus sinensis: A study on the synergistic effect of endophytic fungi and biochar

Article

Author: Zhou, Beibei ; Yao, Shaoxiong

Endophytic fungi (Trichoderma harzianum (TH) and Paecilomyces lilacinus (PL)) showed potential in phytoremediation for soils contaminated with potentially toxic elements (PTEs (Cd and As)). However, their efficiency is limited, which can be enhanced with the assistance of biochar. This study sought to investigate the effects of TH at two application rates (T1: 4.5 g m^-2; T2: 9 g m^-2), PL at two application rates (P1: 4.5 g m^-2; P2: 9 g m^-2), in conjunction with biochar (BC) at 750 g m^-2 on the phytoremediation of PTEs by Miscanthus sinensis (M. sinensis). The results showed that the integration of endophytic fungi with biochar notably enhanced the accumulation of Cd and As in M. sinensis by 59.60 %-114.38 % and 49.91 %-134.60 %, respectively. The treatments T2BC and P2BC emerged as the most effective. Specifically, the P2BC treatment significantly enhanced the soil quality index (SQI > 0.55) across all examined soil layers, markedly improving the overall soil condition. It was observed that T2BC treatment could elevate the SQI to 0.56 at the 0-15 cm depth. The combined amendment shifted the primary influences on plant PTEs accumulation from fungal diversity and soil nutrients to bacterial diversity and the availability of soil PTEs. Characteristic microorganisms identified under the combined treatments were RB41 and Pezizaceae, indicating an increase in both bacterial and fungal diversity. This combination altered the soil microbial community, influencing key metabolic pathways. The combined application of PL and biochar was superior to the TH and biochar combination for the phytoremediation of M. sinensis. This approach not only enhanced the phytoremediation potential but also positively impacted soil health and microbial community, suggesting that the synergistic use of endophytic fungi and biochar is an effective strategy for improving the condition of alkaline soils contaminated with PTEs.

100 Deals associated with Salicylamide/Acetaminophen/Anhydrous Caffeine/Promethazine Methylenedisalicylate

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Indication	Country/Location	Organization	Date
Common Cold	JP	Shionogi Pharma Co., Ltd.	31 Jan 1962

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