High-Altitude Medicinal Plants as Promising Source of Phytochemical Antioxidants to Combat Lifestyle-Associated Oxidative Stress-Induced Disorders

Abstract

Oxidative stress, driven by reactive oxygen, nitrogen, and sulphur species (ROS, RNS, RSS), poses a significant threat to cellular integrity and human health. Generated during mitochondrial respiration, inflammation, UV exposure and pollution, these species damage cells and contribute to pathologies like cardiovascular issues, neurodegeneration, cancer, and metabolic syndromes. Lifestyle factors exert a substantial influence on oxidative stress levels, with mitochondria emerging as pivotal players in ROS generation and cellular equilibrium. Phytochemicals, abundant in plants, such as carotenoids, ascorbic acid, tocopherols and polyphenols, offer diverse antioxidant mechanisms. They scavenge free radicals, chelate metal ions, and modulate cellular signalling pathways to mitigate oxidative damage. Furthermore, plants thriving in high-altitude regions are adapted to extreme conditions, and synthesize secondary metabolites, like flavonoids and phenolic compounds in bulk quantities, which act to form a robust antioxidant defence against oxidative stress, including UV radiation and temperature fluctuations. These plants are promising sources for drug development, offering innovative strategies by which to manage oxidative stress-related ailments and enhance human health. Understanding and harnessing the antioxidant potential of phytochemicals from high-altitude plants represent crucial steps in combating oxidative stress-induced disorders and promoting overall wellbeing. This study offers a comprehensive summary of the production and physio-pathological aspects of lifestyle-induced oxidative stress disorders and explores the potential of phytochemicals as promising antioxidants. Additionally, it presents an appraisal of high-altitude medicinal plants as significant sources of antioxidants, highlighting their potential for drug development and the creation of innovative antioxidant therapeutic approaches.

Keywords: ROS; antioxidant; high-altitude medicinal plants; lifestyle-associated disorders; oxidative stress; phytochemicals.

Figure 1

Oxidative stress-induced health modalities (The illustration was created using BioRender at www.biorender.com).

Figure 2

Source, mechanism of production of ROS leading to oxidative stress and its repercussions along with cellular antioxidant defence. (The illustration was created using BioRender www.biorender.com.) [*: Free radical; Nrf2: Nuclear factor erythroid 2-related factor 2; ARE: Antioxidant Response Element; Mn: Manganese; Cu: Copper; Fe: Iron; OH: Hydroxyl radical; SOD: Superoxide Dismutase; NQO1: NAD(P)H quinone dehydrogenase 1; HO-1: Heme Oxygenase-1; GSTs: Glutathione S-transferases; MDA: Malondialdehyde; TBARS: Thiobarbituric Acid Reactive Substances; ROS: Reactive Oxygen Species; RO: Reactive Oxygen; O₂: Oxygen; Keap1: Kelch-like ECH-associated protein 1; sMaf: Small Maf proteins; H₂O₂: Hydrogen Peroxide].

Figure 3

Endogenous and exogenous sources of antioxidants. (The illustration was created using BioRender www.biorender.com).

Figure 4

Oxidative stress-induced cardiovascular diseases and modulation via phytochemical antioxidants (the illustration was created using BioRender at www.biorender.com). [MAPK: mitogen-activated protein kinase; ROS: reactive oxygen species; JNK: c-Jun N-terminal kinase; p38: p38 mitogen-activated protein kinase; Akt: protein kinase B (PKB); NF-κB: nuclear factor kappa-light-chain-enhancer of activated B cells; AP-1: activator protein 1; oxLDL: oxidized low-density lipoprotein; TBF-α: tumour necrosis factor alpha; PGF2-α: prostaglandin F2 alpha; IL-6: interleukin 6; MDA: malondialdehyde; PARP-1: poly (ADP-ribose) polymerase 1].

Figure 5

Oxidative stress-induced neurodegenerative disease pathology and modulation by antioxidant phytochemicals. (the illustration was created using BioRender at www.biorender.com). [TNFα: tumour necrosis factor alpha, iNOS: inducible nitric oxide synthase, IL-1β: interleukin-1 beta, IL-6: interleukin-6, IL-12: interleukin-12, IL-23: interleukin-23, NMDA: N-methyl-D-aspartate, p65: RelA (a subunit of the NF-κB transcription factor), p53: tumour protein p53].

Figure 6

Antioxidant phytochemicals and modulation of oxidative stress-induced metabolic disorders (obesity and diabetes) (the illustration was created using BioRender at www.biorender.com). [AMPK: AMP-activated protein kinase; SIRT1: sirtuin 1; Nrf2: nuclear factor erythroid 2-related factor; 2NF-κB: nuclear factor kappa-light-chain-enhancer of activated B cells; MAPK: mitogen-activated protein kinase; IRS: insulin receptor substrate; UPR: unfolded protein response; PKC: protein kinase C].