Evaluating Peptides of Picrorhiza kurroa and Their Inhibitory Potential against ACE, DPP-IV, and Oxidative Stress.
Shweta ThakurJyoti ChhimwalRobin JoshiManglesh KumariYogendra PadwadRajiv KumarPublished in: Journal of proteome research (2021)
Picrorhiza kurroa Royle ex Benth. is a high-altitude plant having great medicinal value. However, its medicinal value at the peptide level is still unknown, which limits its utility in the development of peptide-based therapeutics. Here, we identify 65 peptides fromP. kurroa hydrolysate. Sequence analysis suggests that one novel bioactive peptide, ASGLCPEEAVPRR (BP1), has antioxidant potential and shows angiotensin-converting enzyme (ACE) and dipeptidyl peptidase-IV (DPP-IV) inhibitory activities. The molecular docking study showed that BP1 has a lower binding energy and strong affinity toward active pockets of ACE and DPP-IV, which explains its higher ACE [IC50 = 59.90 ± 9.52 μg/mL (43.40 μM)] and DPP-IV [IC50 = 3.04 ± 0.26 μg/mL (2.2 μM)] inhibitory activities. BP1 protects HEK293 cells from H2O2-induced oxidative damage by inhibiting intracellular reactive oxygen species (ROS) and malondialdehyde accumulation and activating the intrinsic antioxidant defense system. Additionally, phase-contrast microscopy studies revealed that pre-treatment of BP1 to HEK293 cells before exposure to H2O2 retains the normal morphology and blocks apoptosis. Furthermore, it also suppresses ROS-induced mitochondrial apoptosis via restoring the mitochondrial membrane potential (ΔΨm) and inhibiting caspase 3/7 activity. Therefore, BP1 has antioxidant potential and ACE and DPP-IV inhibitory activities that could be used for peptide-based formulation(s) in pharmaceuticals to treat diabetes, cardiovascular diseases, and other diseases associated with ROS.
Keyphrases
- oxidative stress
- angiotensin converting enzyme
- diabetic rats
- induced apoptosis
- reactive oxygen species
- angiotensin ii
- dna damage
- cell death
- cell cycle arrest
- molecular docking
- signaling pathway
- cardiovascular disease
- ischemia reperfusion injury
- magnetic resonance
- type diabetes
- endoplasmic reticulum stress
- human health
- drug delivery
- high resolution
- high glucose
- computed tomography
- adipose tissue
- pi k akt
- skeletal muscle
- cardiovascular risk factors
- metabolic syndrome
- single cell
- single molecule
- stress induced
- combination therapy
- coronary artery disease