Mechanistic role and potential of Ayurvedic herbs as anti-aging therapies

Oxidative damage

There are various theories and mechanisms related to the aging process (Figure 1) one of which is the free radical theory. According to this theory, aging can be caused by excessive reactive oxygen species which leads to oxidative damage. There are various external and internal factors that are responsible for the production of reactive oxygen species (ROS) and reactive nitrogen species (RNS). For neutralization of reactive oxygen species, there is a network of exogenous and endogenous antioxidants but still, some ROS/RNS can escape this defensive mechanism. These free radicals have the capacity to harm the body’s healthy cells, which could result in diseases, disorders, or cell damage. Free radicals are responsible for aging and diseases viz. cancer, heart disease, Parkinson’s disease, and also affect the brain and immune system. Oxidative damage by ROS/RNS causes cell dysfunction and physiological damage leads to aging (Figure 2). From this observation, we can conclude that antioxidants are capable of slowing the aging process because they can successfully scavenge ROS/RNS and restrict the oxidative damage.

Figure 1:

Different mechanisms of aging (simple chromosome structure by Prateek Pattanaik, adapted from Wikimedia illustration.png commons is licensed under (CC-BY-SA)).

Figure 2:

Schematic presentation of sources that generate ROS and effect of ROS on different cellular components leads to aging (simple animal cell by Tomas Kebert, adapted from Wikimedia commons is licensed under (CC-BY-SA), Neuron adapted from https://www.freepik.com/free-vector/stem-cell-diagram-white-background_2480958.htm).

Antioxidant enzymes can be used to treat many disorders, such as diabetes, cancer, aging, atherosclerosis, heart failure, and neurological disorders. To assist the body in reducing oxidative damage, antioxidant supplements and meals may be employed. Almost all processed food contains synthetic antioxidants such as BHT and BHA which are formed by the use of chemical antioxidants. Synthetic antioxidants include various classes viz. nitroxides, salens, spin traps, Mn-porphyrin superoxide dismutase, GPX mimetics, etc. Due to new understanding concerning the potential toxicity of synthetic antioxidants as well as customer preferences for natural food additives, the interest in using natural antioxidants to stabilise meals that contain lipids has significantly increased [9]. Propyl gallate and tert-butyl-hydroquinone are the antioxidants that are employed most frequently, which are linked to liver damage and cancer-causing agent in lab animals. Therefore, it is desirable to create and employ more potent antioxidants [10]. Globally, traditional medicine is being re-evaluated due to its fewer side effects. Plants can serve as a source of novel molecules with antioxidant activity since they create an antioxidant effect to combat the oxidative damage brought on by chemicals, sunlight, and reactive oxygen species.

Inflammation

The immune system uses inflammation as a defence mechanism against external intruders. But when it becomes chronic, a number of issues may arise and lead to numerous diseases, including Alzheimer’s disease, cancer, and heart disease. This occurs because the body attacks its own cells. Numerous studies show that elderly people have weaker pro-inflammatory status as compared to younger people which causes chronic inflammation. Inflammaging is the term referring to the low-grade inflammatory condition during the process of aging [11]. Inflammation is an important mechanism of defense mediated by macrophages and monocytes that help in the destruction of microbial pathogens and also repair the injured tissue. However, the inflammatory response becomes chronic, varying critically in the case of age-related diseases and aging. In the tissues of older humans and rodents the level of gene expression related to inflammatory and immune response is considerably higher [12]. Upregulation of NF-κB signaling and high level of serum of IL-6 and TNF-α have also been reported in several age-related studies (Figure 3) [13].

Figure 3:

Schematic presentation of the molecular mechanism of inflammation through activation of Nf-κB signaling during aging.

Telomere shortening

As we age, our bodies gradually lose their physiological function, which impairs cellular integrity and ultimately makes us more susceptible to illness and death. The aging process leads to various ailments like cancer, diabetes, cardiovascular disease, and neurological conditions [14]. Aging is caused by a number of factors, most notably the continual shortening of telomeres that leads to aging. The telomeres gradually shorten with each DNA replication, eventually becoming severely short. The essential enzyme telomerase is involved in protecting and repairing the ends of chromosomes (telomeres). The telomerase activity rate is influenced by a person’s habits as well as environmental factors which can shorten or lengthen life (Figure 4). However, human cells exhibit very low levels of telomerase activity, which accelerates the aging process by causing the shortening of telomere. There are two main causes of telomere shortening that are exogenous and endogenous [15]. Telomere shortening can be cured by different traditional medicine derived from Ayurvedic herbs.

Figure 4:

Telomerase induced aging.

DNA damage

DNA damage can accelerate the aging process by impacting transcription, signalling apoptosis or cellular senescence, telomere shortening and mutations. Telomere shortening ultimately leads to telomere malfunction (chromosome uncapping) and the activation of DNA damage checkpoints, resulting in a permanent cell cycle halt and replicative senescence. The molecular cause of aging is still unclear. DNA has the capacity to repair damage brought on by internal factors like defects in replication process as well as external factors like Ultra Violet radiation and genotoxic medicines in species with various life spans [16], [17], [18]. DNA is damaged due to various factors like mutation and replication halts. This damage prevents the progression of the cell cycle and activates signalling pathways that have an impact on the cell through cellular senescence, death, or repair. The defects in genes cause the accumulation of unrepaired DNA and chromosomal damage [19].

Protein damage

Proteins are the basic component of physiological and cellular processes and the physical and chemical properties of proteins govern their activity. The protein sequence has an impact on biological activity, stability, half-life, protein folding, and final shape. Studies on protein production, quality control, and degradation pathways clearly suggest that maintaining proteostasis is crucial for good health and longevity [19]. The specific activity of many enzymes is decreased by metal-catalysed oxidation, amino acid residue oxidation, and changes brought on by lipid oxidation products. These processes also affect the thermal stability of proteins and raise their carbonyl content [20].

Cell death

The two methods involved in cell death are necrotic cell death mechanisms and energy-dependent programmed cell death apoptosis processes. The body can maintain apoptosis system equilibrium by actively “suicide” of damaged cells. Apoptosis occurs when the cell is not able to repair its damaged DNA and may contribute to diseases and aging process. Apoptosis is crucial for healing of wounds, but it slowed down with age and frequently occurs in association with local inflammation [21]. The correlation between apoptosis and aging can be seen in the central nervous system, where neuronal apoptosis rises with age. Similar to this, declining apoptotic defences causes an increase in cancer rates with aging [22].

Longevity of genes

It was shown that particular genes present in a variety of animals contribute to determining the entire lifetime potential. In fact, the presence of these genes causes the synthesis of products that use a variety of ways to manage the life of the species, increasing metabolic capacity, controlling stress, resistance, and genes that accelerate aging are silenced. According to several studies, it has been observed that the SIR2 gene enhances the longevity of nematodes as well as yeasts [23]. Skin aging is caused by an increase in enzyme activity. These enzymes are elastases, collagenases, and tyrosinase. The cause of external factors which are responsible for aging like prolonged exposure to contaminants or radiation. Internal aging is thought to be established and controlled by a number of inherited genes concurrently [24].

Butea monosperma (palash)

B. monosperma plant belongs to the Fabaceae family. It is a deciduous tree commonly called ‘palash’ or ‘dhak’, ‘flame of the forest’ and has bright orange flowers which are used in traditional medicines. It has anticonvulsive, antistress, antidiabetic, and anti-aging effects. Extracts from B. monosperma exhibit a number of properties such as inflammatory resistance, wound-healing, anticancer and hepatoprotective properties [26]. This plant can be used to cure brain-related diseases like Alzheimer’s disease. Alzheimer’s disease develops due to a decrease in the level of acetylcholine, which is the most significant neurotransmitter in the brain and is hydrolyzed by the enzymes viz. acetylcholinesterase and butyrylcholinesterase. Therefore, it can be concluded that using medicines that can slow down the function of certain enzymes such as acetylcholine (Ach), acetylcholinesterase (AchE) is a beneficial therapeutic approach for treating the symptoms of Alzheimer’s disease. This plant has secondary metabolites like triterpenoids, steroids, glycosides, alkaloids, carbohydrates, and polyphenols (gallic acid, p-Hidroxybenzoic acid, syringic acid, salicylic acid, and ellagic acid). Two of the main phytochemicals found in B. monosperma, isobutrin and butrin, provide the plant its hepatoprotective and antioxidant properties. According to reports, phenolic compounds are vital for stabilizing lipid peroxidation and have antioxidant action [27]. In an animal model, methanol and ethyl extracts from leaves of this plant showed neuroprotective properties [28]. The methanol extract of the stem is beneficial for the treatment of convulsion. Additionally, this plant has anti-aging properties due to its metalloproteinase inhibitory activities along with its anti-inflammatory effects [28].

Phyllanthus niruri (bhumyamalaki)

P. niruri belongs to the family Euphorbiaceae and is popularly used all over the world. It is utilized for skin conditions, diabetes, chest pain, and urinary issues in the Indian Ayurveda and Unani systems. It has a bitter taste, astringent properties, and laxative effects. The results of the phytochemical studies were reported, and it was observed that numerous substances, notably lignans, phyllanthin, hypophyllanthin, flavonoids, glycosinoids, and tannins, were detected. Quercetin, a bioactive compound has anti-cancer, anti-inflammatory, and anti-oxidant, properties. It was said to possess qualities similar to those of Rasa, Guna, and Vipaaka. Ayurveda has mentioned its uses as Daahaghna (refrigerant, relieves burning sensation). Antioxidants play a major role in hepatitis, liver protection, and aging [29]. HPLC analysis revealed the presence of gallic acid, ellagic acid, and corilagin in the plant extract. The aqueous extracts were identified as a good source of natural antioxidants which can be used in cosmetics for skin-antiaging, sun-blocking, and whitening agents. In an experiment, the dexamethasone-suppressed rat treated with plant extract shows improvement in wound healing ability [30]. An extracted protein from P. niruri leaves shows decreased lipid peroxidation in the liver against carbon tetrachloride-induced liver damage and has an antioxidant effect [31, 32]. Moreover, due to the presence of quercetin, there is a significant amount of antioxidant properties in this plant which can be utilized to cure various ailments [33].

Holarrhena antidysenterica (kutaja)

Holarrhena antidysenterica is a member of the family Apocynaceae. It is a small tree or deciduous shrub. According to Ayurveda pods of this plant contains properties like stanyasodhana (a lactodepurant), ama, and asthapanopaga (adjuncts to enema). Sushruta claims that the seeds have diuretic qualities [34]. Some of the secondary metabolites present in this plant are kurchamide, holarrifine, kurcholessine, conessidine, kurchenine, holarrhidine, holarrhessimine, kurchamine, conkurchinine, and akurchilidine [35]. This plant contains bioactive alkaloids such as conessine, which has anti-acetylcholinesterase effects, and can be used to treat Alzheimer’s disease (causes neurodegenerative illness associated with aging and has limited therapeutic options available) [36]. The plant H. antidysenterica, popularly called “Kutaja” is a significant plant that is used as a treatment for various ailments. According to reports, H. antidysenterica’s leaves have antibacterial, anti-inflammatory, and analgesic properties. Methanolic extract of bark showed an analgesic effect on Swiss albino mice and Wistar rats [37]. Methanolic bark extract of this plant shows a decrease in the level of nitric oxide along with malondialdehyde in male albino Wistar rats that had undergone colitis caused by 2,4-dinitrobenzene sulfonic acid. The rats also resisted goblet cell rupture, mucosal layer inflammation, and inflammatory cellular infiltration [38]. The plant’s hydro-methanolic seed extracts also demonstrated prevention of H₂O₂ degradation which shows its antioxidant properties, nitrite production by competing with O₂, deoxyribose breakdown by OH ions which prove to have DNA protection ability of this plant and also resist the process of lipid peroxidation in the ethyl acetate fraction [39, 40].

Picrorrhiza kurroa (katuka)

Picrorrhiza belongs to the family Plantaginaceae. The “Charaka Samhita” and the “Sushruta Samhita” are the two foundational medical treatises of Ayurveda in which Picrorrhiza kurroa is referred to “Kutki” [41]. It exhibits antioxidant, anti-inflammatory, and immunomodulatory properties, its hepatoprotective impact is what makes it so valuable. The leaf extract of P. kurroa has antioxidant and radical-scavenging properties that point to their potential source of natural antioxidants for treating various oxidative stress-related disorders [42]. This plant contains various flavonoids and polyphenolic content which shows an inhibitory impact against free radical-mediated oxidation of BSA (Bovine serum albumin) [43]. By using DPPH assay it has been observed that the extracts of this plant have the potential in scavenging free radicals and inhibit lipid peroxidation [44]. Phenolic components present in Picrorrhiza are vanillic acid, apocynin, picein, androsin, gallic acid, ellagic acid, isocorilagin, and kutkin [45].

Psoralea corylifolia (bakuchi)

P. corylifolia is a member of the family Fabaceae. In Ayurveda, Bakuchi is well-known for its effectiveness against skin conditions, particularly leucoderma. Bakuchi oil is used as a home remedy to treat skin disorders. As a result of its powerful healing ability, its application also helps to reduce boils and skin outbreaks. It also helps to improve hair growth. Bakuchi contains pharmacological activities like anti-inflammatory, antimicrobial, immunomodulatory, antitumor, anti-pregnancy and estrogenic, antimutagenic, antiviral, hepatoprotective, photosensitizing, anti-asthmatic, antifilarial, antiplatelet, osteoblastic, hemostatic, antipyretic, and antidepressant [46]. Psoralen, bakuchiol, and bakuchicin are three main components in bakuchi and other components in Bakuchi include Angelicin, psoralidin, bavachromanol, bavachin, corylinal, bavachalcone, bavachinin, isobavachalcone, psoralenol, neobavachalcone, bavachromene, bavachromeneisopsoralen, neobavaisoflavone, and corylidin. Bakuchiol has antioxidant activity that protects human red blood cells against oxidative haemolysis. Due to the presence of anti-inflammatory properties, coconut oil and bakuchi oil aid to lessen inflammatory reactions on the skin. Retinol takes care of your skin by eradicating wrinkles, fine lines, and dull skin and bakuchiol has gained popularity in recent years due to its effects that are similar to those of retinol. It is the third-strongest form of retinoid, a vitamin A derivative that encourages skin cell renewal and boosts the production of collagen. Bakuchiol helps to calm and cure your skin from the inside out by encouraging cell turnover and healthy cell regeneration [47].

Rauwolfia serpentina (sarpagandha)

R. serpentina belongs to the family Apocynaceae. R. serpentina is used against snake bites. Additionally, a wide range of therapeutic effects of plant extracts have been reported, including antioxidant, antiaging, antihypertensive, and antipsychotic properties [48]. Various alkaloids present in this plant include ajmaline, indobinine, and ajmalimine. The other important phytochemicals include ajmalicine, reserpine, serpentinine, and yohimbine [49, 50]. R. serpentina contains flavonoids that have antioxidant, anti-inflammatory, prevent oxidative cell damage, and anti-cancer activities. The methanolic leaf extract of R. serpentina has demonstrated antioxidant efficacy which shows activities like superoxide scavenging and DPPH radical scavenging. The plant rhizome has an antioxidant activity proved by using the methanolic extract of the rhizome in a rat model of CCl4-induced hepatotoxicity. The ethanolic root extract has hepatoprotective activity [51, 52].

Swertia cordata (kirata tikta)

S. cordata is a member of the Gentianaceae family. It is commonly known as Kirata tikta, which translates to “the bitter plant of the Kiratas” and signifies “bitter,” “pungent,” and “medicinal herb.” Another name used for the Hindu god Shiva is Kirata. It exhibits various important activities like antibacterial, anti-hepatitis and anthelmintic. It possesses strong antioxidant, neuroprotective and anticancer activity. Ursolic acid and mangiferin were reportedly found in the aerial parts of the S. cordata plant. 1,7-Dihydroxy-3,5,8-trimethoxyxanthone and 1-hydroxy-3,5,7,8-tetramethoxyxanthone are also isolated from this plant. Methanolic leaf extract, aqueous root extract and methanolic stem extract show antioxidant activity [53].

Pluchea lanceolata (rasana)

P. lanceolata is a member of the Asteraceae family. Pluchea is a potential Ayurvedic herb used in traditional medicine, particularly that practiced by the Mayan civilization, to treat a variety of illnesses [54]. In Southeast Asia, its tea preparation has been shown to improve hyperglycemia, dyslipidemia, and obesity [55]. It is used to cure various ailments such as bronchitis, piles and cough. It is a major component of the well-known ayurvedic anti-inflammatory decoction “Maharasnadi Qwath”. Rasna is an important anti-arthritis and anti-rheumatic medication.The phytoconstituents present are stigmasterol, caproate, β-amyrin, and α-amyrin. Few triterpenes morentenol, quercetin morentenol acetate, and isorhamnetin are present. Flavonoids present in this plant scavenge free radicals and are potent inhibitors of lipid peroxidation. Quercetin and isorhamnetin have good antioxidant activity and they have the ability to scavenge free radicals [56]. Oral pre-treatment with P. lanceolata extracts at doses of 100 and 200 mg/kg for 7 days was useful against cadmium-induced oxidative stress and genotoxicity in rats. With oral administration of P. lanceolata extract, consecutive days prior to CdCl2 intoxication, significant reductions in malanodialdehyde formation and xanthine oxidase activity, restoration of the activity of antioxidant defence system enzymes like glutathione peroxidise (GPx), glutathione-S-transferase (GTs), glutathione reductase (GR), and catalase (CAT) [57].

Hemidesmus indicus (sariva)

H. indicus is a member of the Apocynaceae family. The entire herb is recommended for treating various diseases such as asthma, cough, abdominal swelling, etc. According to Charaka Samhita, the decoction of Sariva’s leaves is used for the sallow complexion and loss of voice. Active phytochemicals present in the roots of Hemidesmus are Hemindicusin and Hemidesmin-1. Some other important secondary metabolites are lupeol octasonate, sitosterol, hexatriacontane, and β-amyrin acetate. Different parts of H. indicus have oil that contains 80 % of crystalline matter, benzaldehyde, α-amyrin triterpene, β-amyrin triterpene, and hemidesterol [58]. Ethanolic extract of H. indicus showed an increase in the level of antioxidant enzymes and inhibition of cutaneous oxidative stress in rats. Roots possess the ability of free radical scavenging and the aqueous extract of roots shows a decrease in lipid peroxidation index which is ascribed to its antioxidant action. It also shows wound-healing activity [59].

Vetiveria zizanioides (vetiver)

V. zizanioides is a member of the family Poaceae. The whole plant can be used to form various medicines. The essential oil derived from the roots is utilized in cosmetics. Vetiver oil is used as an active component in cosmetics having cosmeceutical benefits, such as brightening, antioxidant, anti-aging, anti-inflammatory, and antimicrobial properties. Khusimol and α-vetivone are the two major components of essential oil. In Ayurveda, this plant is categorized under Varnya. Varnya enhances the skin complexion [60]. V. zizanioides extract was able to restore skin barrier function by increasing skin lipid neosynthesis in reconstructed human epidermis and skin explants. Additionally, it was shown that vetiver extract increased the transfer of lipids and cornification of the epidermis. In both in vitro and ex vivo models, vetiver extract significantly affected adipocyte maturation and adipogenesis [61].

Withania somnifera (ashwagandha)

W. somnifera is a member of the family Solanaceae and is commonly called ashwagandha. The roots are used for longevity by enhancing immunity and delay the aging process. At present, more than 138 withanolides, 13 alkaloids, and several sitoindosides have been isolated from roots and berries [62]. The alkaloids present are ashwagandhine, cuscohygrine, anahygrine, tropine etc. The main active agents in this plant are withaferin A and withanolide A [63]. In the HeLa cell line, ashwagandha root extract was able to improve telomerase enzyme activity. In Caenorhabditis elegans, withanolide, an active ingredient in ashwagandha, extended the average lifespan by 29.7 % and controlled the insulin/IGF-1 signaling pathway and brain functioning [63]. Also, in human peripheral blood cells, anti-genotoxic activity is shown by ashwagandha extract against H₂O₂-induced DNA damage. Thus, W. somnifera root extract provides an anti-aging effect through enhanced telomerase activity [64, 65].

Tinospora cordifolia (guduchi)

T. cordifolia, is also called Guduchi, is an herb that belongs to the Menispermaceae family. Guduchi remarkably has been used in the Ayurvedic medical system since very long time. It is recognised in Ayurveda as a Rasayana medicine that is suggested to boost overall body resistance, encourage longevity, and is also used as an adaptogen and antistress agent. In our traditional Ayurvedic books it is mentioned that this is helpful to cure various ailments such as skin conditions, various types of fever, jaundice, and gout [66, 67]. Guduchi is cardiovascular protective, osteoprotective, neuroprotective, antioxidant, anti-anxiety, anti-microbial, anti-inflammatory, and anti-cancer. This plant contains alkaloids such as berberine, tinosporin, tinosporic acid, tinosporol, diterpenoids, sesquiterpenoids, aliphatic compounds, and essential oil [68, 69]. In a study, the ethanolic extract of stem has used to observe that lymphocytes extracted from Swiss Albino mice showed DNA protective activity. Extract from T. cordifolia showed enhancement in cell viability and protection against cytotoxicity and DNA damage in PC12 cells. Another study employing ethanolic stem extracts using the comet assay found that lymphocytes from Swiss Albino mice were able to protect their DNA from sodium arsenite-induced genotoxicity [65].

Hibiscus sabdariffa (gongura)

H. sabdariffa is a member of the family Malvaceae and is popularly known as Gongura. It is mentioned in Ayurvedic literature that the whole plant is used to form various formulations which cure ailments like liver disorder, hypertension, pyrexia, etc. The phytochemicals present in H. sabdariffa are flavonols, anthocyanins, and protocatechuic acid (PCA). Anthocyanin present in this plant shows antioxidant activity, anticancer activity, and protection against atherosclerosis. Ascorbate and anthocyanins have excellent antioxidant properties. According to several reports, the phytochemical compositions of H. sabdariffa play a major role in collagenase inhibition. Collagenase is a multi-domain enzyme that contains zinc, which degrades collagen [70]. Collagen is a structural protein and component of the extracellular matrix. The collagen fibers deteriorate with time and also from UV radiation, which results in wrinkles and sagging. Therefore, this plant is used to inhibit collagenase enzymes and is used as an anti-aging [71].

Bacopa monnieri (brahmi)

This plant belongs to the family Scrophulariaceae and also known as “Brahmi”, is a nootropic ayurvedic herb called “Medhya Rasayan” and is used to treat neurological disorders. From ancient times it has been used for maintaining longevity and youthful vitality. It shows antioxidant capacity which is responsible for its anti-inflammatory, anti-aging, anti-stress, immune-modulatory, and cognition-facilitatory benefits [72]. According to Ayurveda, its properties are defined as a digestive, laxative, and also used as a tonic for heart and nerves-related disorders [73]. Alkaloids, tannins, flavonoids, saponins, and steroids are the phytochemicals present in Bacopa. The methanol extract of Bacopa exhibits a dose-dependent antioxidant activity and DNA damage protection effect. According to some studies, it has been reported that the Brahmi extracts show superoxide scavenging activity, lowered the cytotoxicity induced by H₂O₂, and also lower the damage to the DNA in fibroblast cells of humans. The methanol extract of Brahmi used in non-immortalized fibroblasts of humans showed protection against cytotoxicity and DNA damage. By using pRSETA plasmid of Escherichia coli a study was conducted that showed a DNA protection effect when the extract of Brahmi was used [74]. Further research on DNA damage caused by sodium nitroprusside (SNP) was significantly inhibited by brahmi extract [75]. Microglia cells of the CNS are primarily responsible for neuroinflammation. Liberation of IL-6, IL-10, TNF-α, and cytokines cause Neuroinflammation which leads to the development of neurodegenerative diseases viz. Alzheimer’s, Parkinson’s, Dementia, etc. Betulinic acid suppressed the LPS-mediated proinflammatory response by downregulating the COX-2 gene expression, and prostaglandin E2 synthesis by modulating Akt and ERK signaling pathways [76]. Brahmi plant extract is reported to reduce the cellular level of Caspase-10 which resulted in the reduction of neuroinflammation [77].

Convolvulus pluricaulis (shankhapushpi)

C. pluricaulis Choisy is a member of the family Convolvulaceae. It is commonly called Shankhapushpi. It contains several types of alkaloids and flavonoids. It also contains coumarins (active chemicals which is responsible for their biological effects) [78]. This herb has the potential to cure depression and various brain-related disorders. They have antidepressant, neurodegenerative, antioxidant, anti-stress, hypolipidemic, and immunomodulatory activity. The phytochemicals present in this herb are volatile oils and fatty alcohols. It contains palmitic acid (66.8 %), myristic acid (30.9 %), linoleic acid (2.3 %) 20-oxodotriacontanol, tetratriacontanoic acid, 29-oxodotriacontanol, Scopoletin, β-sitosterol, and cetyl alcohol are also present. Recent research on the neuroprotective effects of shankhpushpi discovered that it has anti-oxidant and anti-apoptotic capabilities, as well as the ability to protect against H₂O₂-induced cytotoxicity, telomer damage, and plasmid DNA damage. With strong telomerase activator, telomer protecting, and DNA repair characteristics, it proves as a potential anti-aging therapeutic candidate [79].

Glycyrrhiza glabra (yashtimadhu)

Glycyrrhiza glabra, also called Yashtimadhu and belongs to the family Fabaceae. In Ayurveda, G. glabra has been discovered to be in charge of many functions including wound healing, cognitive function enhancement, and cerebroprotective [80]. The phytochemical compounds present in G. glabra are alkaloids, glycosides, proteins, pectin, phenols, flavonoids, steroids, etc. [81]. It shows strong antioxidant, anti-inflammatory, and antiaging activity. This herb is high in glycyrrhizin, a triterpene saponin. It has been shown to improve DNA damage tolerance caused by CdCl₂-induced genomic and ROS damage in human lymph cells [82]. A study shows that extract from this plant protects the microsomal membranes and DNA of pBR322 plasmid from breaking. Another study shows that ethanol extract from this plant was applied at a conc. of 250 g/mL, increased the longevity of the C. elegans model by 14.28 % and the survival rate by 33.56 % [83].

Ocimum basilicum (basil)

O. basilicum also called basil, belongs to the Lamiaceae (mint) family and is an important ayurvedic herb. The phytochemicals present in O. basilicum are polyphenols, quinones, iridoids, di-terpenoids, tri-terpenoids, pyrrolidines, flavonoids, anthocyanins, tannins, coumarins, alkaloids, saponins, insect molting hormones and also include volatile oils which are linalool, methyl chavicol, methyl eugenol, and eugenol [84]. It has been demonstrated that the essential oil of tulsi enhances the effect of the telomerase enzyme and downregulates TERF-1 (telomeric repeat binding factor-1) which has the ability to suppress telomere length. Another species of tulsi namely Ocimum tenuiflorum has bioactive chemicals present in seed extracts that showed strong antioxidant activity and prevent DNA damage in the pBR322 plasmid model [85].

Curcuma longa (haridra)

C. longa is a member of the Zingiberaceae family and is also called Haridra. Since ancient times, turmeric has been a key component of Ayurvedic treatment in India. The Phytochemical components of turmeric have been thoroughly studied by numerous experts. Currently, more than 235 chemicals, mostly phenolic and terpenoids have been found in turmeric, including alkaloids, sterols, monoterpenes, sesquiterpenes, diterpenes, triterpenoids, diarylheptanoids, diarylpentanoids, and phenylpropene. Curcumins, additional curucinoids (diarylheptanoids), and essential oils were the main bioactive components demonstrating a variety of biological actions. In a study, it was shown that DNA protection is promoted by curcumin in the bone marrow of a mouse model [86, 87]. The Nrf2 transcription factor controls enzymes that are responsible for anti-inflammatory activity, antioxidant activity and DNA repair. The activity of these enzymes is enhanced by curcumin when it reacts with Keap1 (kelch like ECH associated protein 1) [88]. Curcumin increased mean longevity in D. melanogaster and C. elegans models by 25.8 % and 25.0 %, respectively [89, 90].

Acorus calamus (vacha)

A. calamus is a member of the Acoraceae family and is also called Vacha or sweet flag. It has been an important Ayurvedic herb that has strong antioxidant and cytoprotective properties. The phytochemicals present in A. calamus are sterols, triterpenoid saponins, triterpene glycosides, sesquiterpenoids, phenylpropanoids, alkaloids, and monoterpenes. Major compounds present in this plant are sesquiterpenoids and phenylpropanoids (primarily asarone and eugenol) [91]. In vitro study showed that it increases DNA repair, and protects DNA from gamma radiation [92].

Semecarpus anacardium (bhallataka or bhilwa)

S. anacardium belongs to the Anacardiaceae family and commonly called bhilwa or bhallataka, is an important ayurvedic medicinal herb. It is also used for other purposes such as marking cloth, hair dye, and other things since ancient times. S. anacardium has many therapeutic uses, the fruit and nut extract have many properties, which are anticarcinogenic, hair growth promoter, anti-inflammatory, antiatherogenic, hypoglycemic, CNS stimulant, anti-reproductive, anti-microbial, and antioxidant [93]. The nut of S. anacardium contains a variety of phytochemicals, including amino acids, vitamins, minerals, bhilawanols, phenolic compound, bioflavonoids, which have a number of therapeutic benefits. The findings of the current research showed that the S. anacardium nut contains superoxide dismutase, peroxidase, tocopherol phenolics and acts as a natural antioxidant [94]. The extracts of S. anacardium substantially (p 0.05) reduced the rise in inflammatory cytokine levels [95].

Centella asiatica (mandukaparni)

C. asiatica is an important ayurvedic herb that is also called Mandukaparni. It is a member of the Apiaceae family. Since ancient times it has been used for rejuvenation and to improve memory. Different parts of the plants contain secondary metabolites like polyphenols, tannins, flavonoids, p-coumaric acid, β-carotene, ascorbic acid, and terpenoids. These metabolites have antimicrobial and important antioxidant properties. The active compounds of C. asiatica are mainly asiaticoside, pentacyclic triterpenes, asiatic, madecassoside, and madecassic acids. The extract of Mandukaparni showed improved cognitive functions in rodent models by enhancing mitochondrial and antioxidant gene expression in the liver and brain [96]. The presence of triterpenoid saponins in the plant extracts may explain how they facilitate the regrowth of skin cells, boost tensile strength of skin and resilience, and also prevent the spread of bacteria [97]. The leaves of Mandukaparni show high antioxidant activity [98]. Recently, researchers found that this plant’s extract has high telomerase activity.

Emblica officinalis (amla)

E. officinalis, also referred to as Indian gooseberry or amla is a member of the Euphorbiaceae family. The phytochemical present in this plant is mainly amino acids, phenols, alkaloids, and tannins. They also contain flavonoids, vitamin C, chebulinic acid, ellagic acid, quercetin, pectin, trigallayl glucose, ellagotannin, pendunculagin, punigluconin, emblicanin A or B, gallic acid, etc. [99]. The biological activity of amla includes antimicrobial, hepatoprotective, cytoprotective, analgesic, antipyretic, anticancer, immunomodulatory and antioxidant, etc. [100]. E. officinalis is well known for boosting immunity because of its high vitamin C concentration [101, 102]. It is a potent source of antioxidants, including polyphenols and these antioxidants give E. officinalis its free radical scavenging potential [103]. The extract of this plant protects the human skin fibroblast from photo-aging due to its high reactive oxygen species scavenging and anti-oxidant capability. It shows the inhibitory action of MM-1, augmentation of Pro-Collagen-1 and hyaluronic acid content as well as prevention of UVB-induced apoptosis [104].

Panax ginseng (ginseng)

P. ginseng belongs to the Araliaceae family and is also called as Korean Red Ginseng. It is an important ayurvedic herb that has powerful skin antiaging agents. This plant has antioxidant, anti-inflammatory, and antiaging activity [105]. Several bioactive components are found in P. ginseng, which are alkaloids, polysaccharides, ginsenosides, phenolic acid, and glucosides [106]. The important phytochemicals present are ginsenosides. The major ginsenosides present are Rg1, Re, Rd, Rc, Rb2, Rb1, and F1, F2, Rh1, Rh2, Rg3 are either absent or present in very small amounts [107]. The antiaging property of Rb1 is due to the formation of (type 1) collagen and suppresses UV induced apoptosis [108]. Human HaCaT keratinocytes were shielded by ginsenoside F1 from apoptosis brought on by UVB radiation. In an experiment, the extract of this plant was used on human dermal fibroblasts cells and hairless mouse shows an inhibitory effect against UVB-induced skin aging [109]. In a study, it was observed that ginseng reduces oxidative stress in rats, which lowers lipid peroxidation and restores antioxidant potential. Aged rats fed with red ginseng water extract displayed significantly less oxidative damage and restored glutathione level. It also increases the level of antioxidant enzymes (heme oxygenase-1 and nuclear factor erythroid-2 related factor 2) [110].

Nordostachys jatamansi (jatamansi)

N. jatamansi DC. also called jatamansi, belongs to the Valerianaceae family. It is used in Ayurveda as a tonic, stimulant, and disinfectant. It also treats heart disease, hypertension, hyperlipidemia, and mental disorders. Both norepinephrine and serotonin levels in the brain can be decreased by jatamansi [111]. It possesses antibacterial, antifungal, antiviral, and antioxidant properties. According to phytochemical investigations, the plant roots produce an essential oil that contains sesquiterpenes and coumarins. The main sesquiterpene is jatamansone or valeranone. There are other sesquiterpenes present, which include, nardosinone, jatamol A, jatamansinol, jatamansinone, nardostachone, jatamol B, and many more [112, 113]. There have also been reports of the alkaloid actinidine [114]. N. jatamansi helps to increase skin elasticity and remove wrinkles by enhancing the production of collagen and elastin fibers. It is used in pastes and oils to enhance the overall health of the skin and also improves complexion. Significant antioxidant activity can be shown in N. jatamansi ethanol extract. It improves the overall skin complexion and skin health. It is a good source of natural antioxidant. Study showed that natural antioxidant has positive effect on the skin, protect skin sunburn, stop skin aging and also protect from skin cancer [115].

Aloe vera (ghritkumari)

A. vera belongs to the family-Asphodelaceae. Aloe is a perennial, xerophytic succulent plant having a wide distribution. In India, it is found mainly in Gujarat, Rajasthan, and dry regions of Maharashtra, Tamil Nadu and Andhra Pradesh. It is also grown as an indoor plant for decorative purposes. In Sanskrit, Aloe Vera is called Ghrita-Kumari, which means “young girl”. Aloe is a rejuvenating herb that is included under the Rasayana, a special class of Ayurvedic herbs. It is believed to improve the balance between Vatta, Pitta and Kapha-the three main doshas/energy systems in Ayurveda that decide the longevity at cellular level. A wide variety of active metabolites present in this plant include anthrones and anthraquinones, acetylated mannans, polymannans, anthraquinone c-glycosides, lectins etc. The inflammatory response is suppressed by aloin and aloe-emodin inhibits the iNOS and COX-2 expression. In d-glucose induced aging study, aloin reduced the level of inflammatory mediators TNF-α, IL-1β and IL-6 by downregulating the signaling of proinflammatory NF-κB and phosphorylation of p38 and ERK [116]. Hyaluronic acid (HA), a constituent of the extracellular matrix, plays an important role in regulating the inflammatory response. HA present underneath the waxy cuticle in A. vera leaves is used in the commercial preparation of several antiaging cosmetic products [117]. A. vera hyaluronan regulates the inflammatory response by controlling the release of inflammatory cytokines, inflammatory gene expression, and inflammatory cell recruitment [118].