Systems pharmacology based approach to investigate the in-vivo therapeutic efficacy of Albizia lebbeck (L.) in experimental model of Parkinson’s disease

Abstract

BackgroundParkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by loss of dopaminergic neurons in substantia nigra pars compacta and clinically manifested mainly with motor dysfunctions. Plants are rich source of medicinally important bioactive compounds and inhabitants of underdeveloped countries used plants for treatment of various ailments. Albizia lebbeck has been reported to possess antioxidant and neuroprotective properties that suggest the evaluation of its traditional therapeutic potential in neurodegenerative diseases.The aim of present study was to validate the traditional use of Albizia lebbeck (L.) and delineate its mechanism of action in PD. The systems pharmacology approach was employed to explain the Albizia lebbeck (L.) mechanism of action in PD.MethodsThe haloperidol-induced catalepsy was adopted as experimental model of PD for in-vivo studies in wistar albino rats. The systems pharmacology approach was employed to explain the Albizia lebbeck (L.) mechanism of action in PD.ResultsIn-vivo studies revealed that Albizia lebbeck improved the motor functions and endurance as demonstrated in behavioral studies which were further supported by the rescue of endogenous antioxidant defense and reversal of ultrastructural damages in histological studies. System pharmacology approach identified 25 drug like compounds interacting with 132 targets in a bipartite graph that revealed the synergistic mechanism of action at system level. Kaemferol, phytosterol and okanin were found to be the important compounds nodes with prominent target nodes of TDP1 and MAPT.ConclusionThe therapeutic efficiency of Albizia lebbeck in PD was effectively delineated in our experimental and systems pharmacology approach. Moreover, this approach further facilitates the drug discovery from Albizia lebbeck for PD.

Haloperidol‐induced catalepsy as an animal model for parkinsonism: A systematic review of experimental studies

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Anti-Parkinson’s Activity of Tribulus terrestris via Modulation of AChE, α-Synuclein, TNF-α, and IL-1β

“…Catalepsy is the inability of animals such as rodents to correct externally imposed position or posture. The previously elucidated method 41 was followed for the determination of catatonia induced by haloperidol (1 mg/kg i.p.). Cataleptic behavior was observed for 30 to 120 min after the administration of haloperidol by the standard bar test (with 3 and 9 cm elevated bars).…”

A Comprehensive Insight into the Phytochemical, Pharmacological Potential, and Traditional Medicinal Uses of Albizia lebbeck (L.) Benth.

“…The anti-Parkinson activity was evaluated by performing behavioral and biochemical oxidative stress assay in Wistar albino rats. It was observed that the plant extract can be able to ameliorate motor function and prevent biochemical damage in brain cells [ 12 ].…”

“…It is a deciduous tree that is mostly found in the garden or along the roadside and grows from sea level to 1500 m elevation, attaining height up to 18 m. A. lebbeck contains numerous phytochemicals related to alkaloids, anthraquinones, essential oils, flavonoids, glycosides, phenolics, phytosterol, saponins, steroids, and triterpenoids [ 9 – 13 ]. According to various pharmacological studies, this species exhibited excellent antinociceptive, anti-inflammatory [ 11 ], anticancer [ 9 ], antimalarial [ 14 ], antiallergic [ 15 ], antihyperglycemic [ 16 ], antidiabetic [ 17 , 18 ], wound healing [ 19 ], nootropic [ 20 ], and neuroprotective activities such as anti-Parkinson's and anti-Alzheimer activities [ 12 , 21 ]. Furthermore, zinc oxide nanoparticles synthesized from Albizia lebbeck stem bark extract caused concentration-dependent organoprotective effect by changing mean body weight, alanine aminotransferase, serum alkaline phosphatase, urea, creatinine, bilirubin, protein, globulin, albumin, total cholesterol, triacylglycerol, and low- and high-density lipoprotein [ 22 ].…”