Evaluation of antiparkinson activity of methanolic extract of Hyoscyamus niger L. seeds & Curcumin combination in Swiss albino mice

Aim: “Evaluation of antiparkinson activity of methanolic extract of Hyoscyamus niger L. seeds & Curcumin combination in Swiss albino mice.” Objective: To evaluate the antiparkinson activity of a combination of methanolic extract of Hyoscyamus niger L. seeds (MEHN) and Curcumin in a haloperidol-induced parkinsonism in Swiss albino mice by behavioral models, biochemical estimation, histopathology of brain tissue, statistical analysis. Methods: Parkinsonism induced in male Swiss albino mice. Animals were divided into 8 groups (n=6). Group-1 Normal control group received (1% Tween 80, 0.25ml/kg p.o.), Group-2 served as disease control (Haloperidol 1mg/kg i.p.), Group-3 as a standard control (syndopa 10mg/kg p.o.), Group 4 & 5 treated as individual dose (MEHN-500 mg/kg, p.o. & Curcumin-200mg/kg, p.o.), Group 6, 7 & 8 treated in combinations (MEHN (30%)- 150 mg/kg, p.o. + Curcumin(70%)-140 mg/kg, p.o. = 290 mg/kg, p.o. ), (MEHN (50%)-250 mg/kg, p.o. + Curcumin (50%)-100 mg/kg, p.o.= 350mg/kg p.o.), (MEHN (70%)-350 mg/kg, p.o. + Curcumin(30%)-60 mg/kg, p.o.= 410mg/kg p.o.). Dopamine levels in brain tissue were measured, and histopathological analysis was performed on brain tissue. Phytochemical screening of extracts was conducted. The dose-dependent effects were statistically analyzed using ANOVA followed by Tukey-Kramar multiple comparison test. Results: The combination of MEHN and curcumin demonstrated a significant protective effect against haloperidol-induced motor impairments. The treated group 30:70 combination of MEHN and curcumin showed significantly reduced catalepsy scores and improved locomotor activity as compare to disease control group and other individual treatment and combination treatment group. Histopathological studies revealed neuroprotection in the substantia nigra. Neuroprotective effect due to presence of alkaloids (hyoscyamine, hyoscine and scopolamine), flavonoids (rutin, quercetin, and kaempherol), (0.03% of L-DOPA). MEHN reported as to possess dopaminergic, acetylcholine, antioxidant, anti-inflammatory activity. Curcumin, the major polyphenolic component from Curcuma longa reported as crosses the blood brain barrier and has acetylcholine, anti-oxidant, anti-inflammatory property. Curcumin possessed activities for management of PD symptoms, which reduced cataleptic time and increased locomotor activity in treatment group as compared to disease control group. Curcumin has decreased intracellular ROS production, and prevented from alpha-synuclein aggregation. Curcumin has reported to prevent protein activity from inflammatory cytokines transcription factor NF-alphaB, pro-inflammatory cytokines (TNF-alpha, IL-1B, and IL-1alpha), and increased BDNF-alpha activity. It activates PI3K/AKT pathway in the brain. Several curcumin-associated targets identified in PD, including (HSP90AA1, TP53, MAPK1, AKT1, GSK3B, MAPT, STAT3, and SIRT1). Results strongly support neuroprotective effects through PI3K/AKT activation. Conclusion: The combination of Hyoscyamus niger L. seed extract and Curcumin exhibits potent antiparkinsonian activity in experimental mice, with dopaminergic, anticholinergic, antioxidant, anti-inflammatory, and neuroprotective mechanisms of Hyoscyamus niger L. and Curcumin. The combination shows synergistic activity on PD. Their complementary mechanisms modulation of cholinergic/dopaminergic systems and oxidative stress support their potential as safer alternatives to conventional PD therapies.