||| Bangladesh Journal of Pharmacology |||

Tangeretin suppresses HER2-driven breast cancer via PI3K/AKT/mTOR inhibition and caspase-dependent apoptosis

Jaggareddygari Shruthi Reddy, Puligilla Shankaraiah — Tue, 03 Mar 2026 00:00:00 +0000

Tangeretin, a citrus-derived polymethoxylated flavone, exhibits potent and selective anti-cancer activity against HER2-positive breast cancer. It demonstrated cytotoxicity in SKBR3 cells (IC₅₀ = 19.5 ± 1.7 µM) and MCF-7 cells (IC₅₀ = 36.2 ± 2.4 µM), while sparing non-tumorigenic MCF-10A cells (>90% viability; IC₅₀ = 327.5 ± 18.2 µM). Tangeretin markedly reduced clonogenic survival (51.4 ± 3.1 colonies in SKBR3; 78.1 ± 3.7 in MCF-7) and induced pronounced apoptosis, as evidenced by late apoptotic staining (50.6 ± 2.3%), DNA laddering, and strong activation of caspase-3/7 (3.4 ± 0.1-fold) and caspase-9 (2.9 ± 0.1-fold). Flow cytometry revealed significant G₂/M phase arrest in SKBR3 cells (38.9 ± 2.0%). Mechanistically, tangeretin suppressed AKT kinase activity (0.4 ± 0.04-fold), comparable to MK-2206 (0.3 ± 0.0-fold), and reduced the expression of phosphorylated HER2 (p-HER2), p-PI3K, p-AKT, p-mTOR, p-p70S6K, and cyclin D1. These findings establish tangeretin as a selective HER2-targeted anti-cancer candidate that acts through dual inhibition of the PI3K/AKT/mTOR pathway and induction of mitochondrial apoptosis.

Anti-arthritic activity of Alternanthera paronychioides through suppression of inflammatory cytokines and NF-κB signaling

Mehnaz Ghulam Nabi, Naureen Shehzadi, Muhammad Tanveer Khan, Khalid Hussain — Tue, 03 Mar 2026 09:38:14 +0000

Alternanthera paronychioides is traditionally used for managing inflammatory disorders; however, its anti-arthritic efficacy and underlying mechanisms remain insufficiently characterized. The present study evaluated the anti-arthritic potential of A. paronychioides in acute and chronic animal models of arthritis. Previously, sequential extracts were assessed for inhibition of protein denaturation, proteinase activity, and erythrocyte membrane destabilization. The most active n-hexane extract was further investigated in carrageenan-induced inflammation and complete Freund’s adjuvant-induced arthritis in rats. n-Hexane extract treatment significantly reduced paw edema, arthritic severity, hyperalgesia, and allodynia, while improving histopathological, and radiographic outcomes. Molecular analysis revealed marked suppression of pro-inflammatory mediators, including TNF-α, IL-1β, IL-6, NF-κB, and COX-2, alongside up-regulation of IL-4. These findings demonstrate that A. paronychioides exerts potent anti-arthritic effects through multi-target immunomodulation.

2-Methoxy-6-acetyl-7-methyljuglone, a natural naphthoquinone from Polygonum cuspidatum, protects against 6-OHDA-induced neurotoxicity in PC12 cells

Yuanfeng Fu, Weifeng Xu, Dongmeng Liu, Jiaolin Bao, Ren-Bo Ding — Tue, 03 Mar 2026 09:37:43 +0000

This study investigated the neuroprotective effects of 2-methoxy-6-acetyl-7-methyljuglone (MAM, a compound isolated from Polygonum cuspidatum) in 6-hydroxydopamine (6-OHDA)-injuried pheochromocytoma (PC12) cells. 6-OHDA treatment significantly induced cell death, apoptosis and mitochondrial membrane potential loss. MAM pretreatment significantly rescued PC12 cell viability, inhibited the 6-OHDA-induced apoptosis and depolarization in mitochondrial membrane potential. Results also demonstrated that 6-OHDA significantly induced ERK and NF-κB phosphorylation, while MAM pretreatment markedly reduced the 6-OHDA-elevated ERK and NF-κB phosphorylation levels. This suggested that MAM exerted neuroprotective effects likely by suppressing ERK-related oxidative stress and NF-κB-mediated neuroinflammation, thereby protecting neuronal cells from 6-OHDA-induced apoptosis. Collectively, these results suggested that MAM exerted a neuroprotective effect in 6-OHDA-induced Parkinson’s disease cell model by suppressing ERK and NF-κB-mediated apoptotic mechanisms.

Effectiveness of Artemisia pallens against behavioral depression and impact on monoaminergic and GABAergic systems

Deorao Madhaorao Awari, Rajendra O. Ganjiwale — Tue, 03 Mar 2026 09:36:48 +0000

Depression is characterized by decreased monoamine levels (dopamine, noradrenaline, serotonin), gamma-aminobutyric acid (GABA), elevated corticosterone, and dysregulation of the hypothalamic-pituitary-adrenal axis. This study aims to examine the effects of Artemisia pallens against behavioral depression in mice using the tail suspension test. Mice were divided into several groups and received different concentrations of ethyl acetate fractions of A. pallens. The duration of immobility of mice, brain levels of monoamines, GABA, and plasma corticosterone concentration were estimated. Extract (400 mg/kg) significantly (p<0.001) reduced immobility time and increased brain monoamines, GABA levels, and decreased plasma concentration of corticosterone compared to the control group. These findings suggest that A. pallens exhibits significant antidepressant-like activity, likely due to the restoration of the hypothalamic-pituitary-adrenal axis, enhanced brain monoamine and GABA levels, and reduced plasma corticosterone levels.

Neuroprotective effect of juglone against 6-OHDA-induced neurotoxicity in PC12 cells

Qingqing Liu, Jiaolin Bao, Ren-bo Ding — Tue, 03 Mar 2026 09:35:45 +0000

No abstract