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JOURNAL OF ETHNOPHARMACOLOGY · 2023 · IF 5.4

Extraction optimization and constituent analysis of total flavonoid from Hosta plantaginea (Lam.) Aschers flowers and its ameliorative effect on chronic prostatitis via inhibition of multiple inflammatory pathways in rats

Li Yang,Fengxiang Zhang,Weiwei He,Boyuan Zhao,Ting Zhang,Shang Wang,Lifen Zhou,Junwei He

Ethnopharmacological relevance Hosta plantaginea (Lam.) Aschers flowers (HPF) are well-known for their high flavonoid content, which contribute to their widely as traditional Chinese medicine for alleviating inflammation. Despite their recognized potential, information regarding the total flavonoid (TF) of HPF and its therapeutic application in treating chronic prostatitis (CP) remains unknown. Aim of the study We aimed to investigate the extraction optimization, constituent analysis, and alleviating effect of TF on CP as well as its potential mechanism. Materials and methods The optimized extraction of TF from HPF was explored using response surface methodology with a Box-Behnken design model. The major flavonoids in TF were identified based on UHPLC-MS approach. Efficacy of TF (25 and 100 mg/kg, p.o.) on CP was evaluated in prostate antigen emulsion-induced autoimmune CP rat model by measuring prostatic index, the levels of leukocytes and lecithin bodies, as well as histopathological examination. The protein expression contents were detected by western blotting . Additionally, the antioxidant (DPPH and ABTS) and anti-inflammatory (cyclooxygenase 2, COX-2 inhibitory) effects of TF were also evaluated in vitro . Results The optimized conditions for TF extraction were determined as 60% ethanol concentration, 30 mL/g liquid-to-solid ratio, 30 min extraction time, and 90 °C extraction temperature, and the extraction ratio is 65.98 ± 2.14%. A total of 15 major flavonoids in TF were characterized by comparison with reference standards. TF ameliorated the efficacy of CP in rats in a dose-independent manner, including reduced prostatic index and leukocytes levels, elevated lecithin body levels, ameliorated histopathological damage to prostate, and suppressed phosphorylated protein expressions of nuclear factor kappa-B (NF-κB) p65, inhibitor of NF-κB alpha (IκBα), c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase (Erk), just another kinase 1 (JAK1), signal transducer and activator of transcription 3 (STAT3), phosphoinositide 3-kinase (PI3K) and protein kinase B (Akt). Simultaneously, the IC 50 of TF to DPPH, ABTS radicals, and COX-2 were 2.02, 1.79, and 0.0838 mg/mL, respectively. Conclusions We first demonstrated that TF from HPF represents a promising candidate to alleviate CP through suppression of NF-κB, MAPKs, JAK-STAT, and PI3K-Akt signaling pathways.

研究领域: 药理学 · 植物化学 · 炎症研究
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Small · 2023 ·Vol. 19 ·期 17 ·2206936 · IF 13.3

Rapidly Blocking the Calcium Overload/ROS Production Feedback Loop to Alleviate Acute Kidney Injury via Microenvironment-Responsive BAPTA-AM/BAC Co-Delivery Nanosystem

Jiahui Yan,Yanan Wang,Jingwen Zhang,Xiaohu Liu,Liangmin Yu,Zhiyu He

Calcium overload and ROS overproduction, two major triggers of acute kidney injury (AKI), are self-amplifying and mutually reinforcing, forming a complicated cascading feedback loop that induces kidney cell “suicide” and ultimately renal failure. There are currently no clinically effective drugs for the treatment of AKI, excluding adjuvant therapy. In this study, a porous silicon-based nanocarrier rich in disulfide bond skeleton (<50 nm) is developed that enables efficient co-loading of the hydrophilic drug borane amino complex and the hydrophobic drug BAPTA-AM, with its outer layer sealed by the renal tubule-targeting peptide PEG-LTH. Once targeted to the kidney injured site, the nanocarrier structure collapses in the high glutathione environment of the early stage of AKI, releasing the drugs. Under the action of the slightly acidic inflammatory environment and intracellular esterase, the released drugs produce hydrogen and BAPTA, which can rapidly eliminate the excess ROS and overloaded Ca 2+ , blocking endoplasmic reticulum/mitochondrial apoptosis pathway (ATF4-CHOP-Bax axis, Casp-12-Casp-3 axis, Cyt-C-Casp-3 axis) and inflammatory pathway (TNF-α-NF-κB axis) from the source, thus rescuing the renal cells in the “critical survival” state and further restoring the kidney function. Overall, this nanoparticle shows substantial clinical promise as a potential therapeutic strategy for I/R injury-related diseases.

CAS / MDL: 63449-41-2 126150-97-8
研究领域: 纳米技术 · 药学 · 肾脏生理学 · 分子生物学 · 治疗学
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CHEMICAL ENGINEERING JOURNAL · 2021 · IF 13.273

Metformin-hydrogel with glucose responsiveness for chronic inflammatory suppression

Dandan Zheng,Wei Chen,Huitong Ruan,Zhengwei Cai,Xiuyuan Chen,Tongtong Chen,Yuhui Zhang,Wenguo Cui,Hao Chen,Hongxing Shen

Diabetes-induced chronic inflammation accelerates tissue degeneration and is difficult to cure due to the persistent pathological high-glucose microenvironment. Herein, a glucose-responsive drug delivery system was constructed by conjugating phenylboronic acid on the surface of liposomes via membrane insertion and further crosslinked into a glucosamine-modified hydrogel composed of hyaluronic acid (HA) and poly(ethylene glycol) diacrylate (PEG) through borate linkages to deliver metformin, which could achieve the anti-inflammation effect under high glucose condition ( [email protected] ).The release kinetics results revealed that [email protected] could adjust the amount of metformin by responding to the change of glucose concentrations. It is proved that [email protected] could protect mitochondria from ROS, thereby inhibiting the activation of the NLRP3 inflammatory pathway and finally increasing the synthesis of extracellular matrix (ECM) in the nucleus pulposus cells compared to the high glucose-treated group. In vivo experiments showed that [email protected] could effectively promote tissue regeneration in the diabetes-induced intervertebral disc degeneration model rats by inhibiting high glucose-induced chronic inflammation and stimulating ECM synthesis. Overall, a drug delivery system with glucose sensitivity was designed to achieve the spatiotemporal release of metformin, the long-term anti-inflammation and promotion of ECM synthesis which ensures the smooth completion of tissue regeneration under diabetic conditions.

研究领域: 药学 · 生物医学工程 · 材料科学 · 糖尿病研究 · 炎症生物学
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