|
 
 |
| REVIEW ARTICLE |
|
| Year : 2023 | Volume
: 8
| Issue : 1 | Page : 3-18 |
|
A review on the protective role of selected Ayurveda herbs against skin cancer
Aniqa Aniqa, Sarvnarinder Kaur, Shilpa Sadwal
Department of Biophysics, Panjab University, Chandigarh, India
| Date of Submission | 01-Apr-2022 |
| Date of Acceptance | 18-Aug-2022 |
| Date of Web Publication | 30-Dec-2022 |
Correspondence Address:
Dr. Sarvnarinder Kaur
Department of Biophysics, Panjab University, Chandigarh 160014
India
 Source of Support: None, Conflict of Interest: None
DOI: 10.4103/jdras.jdras_45_22
Melanoma skin cancer (MSC) is considered the most aggressive among all skin cancers due to its tendency to fast growth, metastasis, and high relapse rate. Although MSC is treatable if identified early, several side effects and aesthetic issues associated with its treatment impose a psychological burden and compromise patients’ quality of life. Thus, there is a dire need for primary prevention by adopting alternative remedies, which are accessible, safe, and cost-effective. The present review emphasizes the role of selected Ayurveda herbs, viz., Azadirachta indica A. Juss, Ocimum tenuiflorum L., Phyllanthus emblica L., Santalum album L., Tinospora cordifolia (Willd.) Hook. F. and Thoms., and Withania somnifera L. Dunal, which are long being utilized in the Indian traditional system to tackle diverse health problems in preventing MSCs. PubMed and Google Scholar were used to search various research articles on the anti-oncogenic and chemopreventive roles of Ayurveda herbs. This review emphasizes the beneficial effects of Ayurveda herbs so that the ordinary public includes these herbs in their routine to prevent MSC and other cancers. The available literature clearly states that these herbs are beneficial in preventing MSCs. However, the scarcity of clinical trials on these herbs warrants extensive research in this area to obtain an efficacious drug. Keywords: Ayurveda herbs, cancer in Ayurveda, chemoprevention, melanoma skin cancer
How to cite this article:
Aniqa A, Kaur S, Sadwal S. A review on the protective role of selected Ayurveda herbs against skin cancer. J Drug Res Ayurvedic Sci 2023;8:3-18 |
How to cite this URL:
Aniqa A, Kaur S, Sadwal S. A review on the protective role of selected Ayurveda herbs against skin cancer. J Drug Res Ayurvedic Sci [serial online] 2023 [cited 2023 Mar 26];8:3-18. Available from: http://www.jdrasccras.com/text.asp?2023/8/1/3/366295 |
| Introduction | |  |
A virtual environmental interface, the skin, covers almost 16% of the body mass and protects our internal organs from various assaults.[1] The skin comprises three layers epidermis, dermis, and hypodermis. The epidermis (ectodermal origin) acts as the body ’s armor, a physiochemical barrier against environmental stressors.[2],[3],[4],[5],[6],[7] Keratinocytes (tightly connected by desmosomes and tight junctions) are abundant in this layer. Dermis (mesoderm origin) underlies the epidermis and anchorages several appendages (hair follicles, nerves, sebaceous glands, and sweat glands). Immune cells and fibroblasts are abundant in this layer and are involved in many physiological responses in the skin.[2],[8] Keratinocyte stem cells in the basal layer of the epidermis divide and differentiate as they migrate outward through the skin’s surface to eventually form corneocytes (tightly linked dead but undamaged cells), constituting the principal barrier of the epidermis.[8],[9]
Because the skin is the most exposed organ of the body, UV rays, noxious agents, and toxicants can damage it. These harmful factors initiate molecular and biochemical stress, causing genomic alterations in skin cells and leading to skin carcinogenesis. The transition of human skin cells into malignant form is a multistep process involving initiation, promotion, and progression that are believed to be activated by oxidative stress in cells, causing transformation (into cancer), survival, and metastasis. Exposure to ultraviolet radiation (UVR) is considered a prominent factor for skin cancer. UVA (315 – ; 400 nm, produces reactive oxygen species), UVB (280 – 315 nm, causes DNA mutations by covalently binding the adjacent pyrimidine base pairs C-T, CC-TT transition), and the atmospheric ozone layer absorb most of the UVC (100 – 280 nm). UVB is the most potent in causing direct DNA damage, oxidative stress, and immunosuppression. The inherent DNA repair mechanism of the cell is thought to repair the UVR-induced DNA damage. However, the cell will undergo irreversible DNA mutations if DNA damage remains unrepaired due to any sporadic or genetic factor. In addition, skin cancer incidence increases significantly with age.[2]
Skin cancers are the most common malignancy of humans, particularly in the Caucasian population, with over a million cases detected each year.[10],[11] However, people of color, viz., Asians, Africans, and Hispanics, also have a higher frequency and prevalence of the disease.[12] The highest skin cancer incidence rate has been reported in New Zealand and Australian individuals and the lowest in Africa. In Asia, the highest incidence of skin cancer cases is recorded in Kazakhstan, with a 23.3 / 100, 000 population.[13]
The three most familiar types are basal cell carcinomas (BCCs), squamous cell carcinomas (SCCs) (referred to as non-melanocytic skin cancer — NMSC), and cutaneous malignant melanoma (CM) [also designated as malignant melanoma (MM) or melanoma].[14],[15], [16],[17] According to a US estimate, approximately one in five Americans will develop skin cancer.[2],[18],[19] They account for nearly 15, 000 deaths and more than three billion dollars annually in medical costs in the USA.[2],[20] NMSC, also known as “ ;cancer of keratinocytes,” is among the most common human malignancies and is mainly classified as BCC and SCC, which account for about 99% of all NMSCs. Other rare forms of NMSCs include Merkel cell carcinoma, sebaceous gland carcinoma, dermatofibrosarcoma protuberans, and angiosarcoma.
Although site-specific treatments are effective in skin cancer, they have some limitations (aesthetic issues, viz., pigmentary changes, atrophy, fibrosis, and cost-burden), which compel researchers to develop novel and potential treatment strategies with minimal side effects. Moreover, the treatment available for metastatic tumors has many adverse effects such as weekend immunity, hair/weight loss, fatigue, sleep disturbances, fertility problems, and morbidity, which cause psychological problems in cancer survivors and decrease their quality of life. It is noteworthy that even after several therapy sessions, a high relapse rate (due to inevitable exposure to UV radiation, environmental toxicants, and chemoresistance) brings a financial burden along with significant morbidity to the patients. Moreover, healthy individuals are also at high risk of skin cancer due to the continuous rise in UV rays and environmental pollutants. So, considering the aforementioned pitfalls, which prove an obstacle, presses the need for alternatives to prevent skin cancer. Therefore, emphasis is on prevention strategies in professional and public education. In addition, early detection and treatment methods are becoming more critical.[21]
Rather than taking medications separately, people prefer foods with desired health benefits.
The literature survey revealed that 80% of the developing countries use alternative/traditional medicine as primary health care.[22] Moreover, alternative medicine continues to gain popularity as a complementary way of care in developed (or industrialized) countries. In countries like India and Pakistan and other eastern developing countries, we see the practice of complementary alongside allopathic medicines, where several healing traditions stand out, such as Ayurveda and Sowa-Rigpa. Notably, these traditions embark on using several therapies using a complex of herbs and plants such as Haridra, Amla, Tulsi, Guduchi, and Nimba.[23] These mixtures nowadays represent the basis for many commercial products used in cosmetics, soaps, toothpaste, and pest repellents. By tradition, they continue as treatments for chickenpox, fever, headache, leprosy, jaundice, constipation, respiratory problems, rheumatism, and gastrointestinal disorders.[23] In this review, we are discussing the preventive efficacy of Azadirachta indica A. Juss (Nimba), Ocimum tenuiflorum L. (Tulsi), Phyllanthus emblica L. (Amalaki), Santalum album L. (Chandana), Tinospora cordifolia (Willd.) Hook. F. and Thoms. (Guduchi), and Withania somnifera L. Dunal (Ashwagandha) against MSCs. The rationale behind selecting these herbs is their easy availability and their importance in Ayurveda medicine system to tackle many skin disorders.
| Materials and Methods | | |
Electronic databases including PubMed, Google Scholar, and Scopus were searched using the keywords (“ Skin cancer ” OR “skin neoplasm ” OR “melanoma ” OR “malignant melanoma ”) AND (“plant” OR “extract” OR “herb” OR “phytochemical ” OR “Azadirachta indica” OR “Ocimum tenuiflorum” OR “Phyllanthus emblica” OR “Santalum album” OR “Tinospora cordifolia” OR “Withania somnifera”). To find relevant studies, articles were primarily screened on the basis of titles and abstracts. To confine the search, only English language papers were included in this review. Inclusion criteria were herbal plants assessed in in-vitro as well as in-vivo studies, which focussed on the preventive as well as metastasis-related mechanisms of MSCs. The collected data have been tabulated systematically in [Table 2]-7].
The rationale behind using A. indica A. Juss (Nimba), O. tenuiflorum L. (Tulsi), P. emblica L. (Amalaki), S. album L. (Chandana), T. cordifolia (Willd.) Hook. F. and Thoms. (Guduchi), and W. somnifera L. Dunal (Ashwagandha) is their easy accessibility, minimal or no side effects, and importance in Ayurveda medicine system to treat various skin disorders.
| Discussion | | |
Melanoma skin cancer (MSC)
MSC is the most destructive form of cutaneous malignancy. MSC (arise from epidermal melanocytes) is often a treatment-refractory and metastasis-prone malignancy. As it proliferates and metastasizes to lymph nodes and other organs [as shown in [Figure 1]], it is regarded as the most lethal of all skin cancers if not diagnosed or treated early.[60] Its incidence has amplified gradually and significantly over the last several decades.[2] Most frequently, melanoma is found on the trunk of men and lower legs of women, although it can occur on the head, neck, mucosal surfaces such as gastrointestinal sites, genital mucosa, oral cavity, eyes, or elsewhere.[61] | Figure 1: Different stages of carcinogenesis: initiation, promotion, and progression. Different chemopreventive agents could interfere with these stages, such as initiation (blocking agents) or steps of promotion and progression (suppressing agents)
Click here to view |
Mutation (valine-to-glutamine substitution at position 600) in the v-RAF murine sarcoma viral oncogene homolog B1 (BRAF) gene encodes a serine/threonine-protein kinase, which is the driving force that triggers the RAS –RAF –mitogen-activated protein kinase (MAPK) pathway, culminating into MSC. A loss or inactivating mutations of the cyclin-dependent kinase inhibitor 2 A (CDKN2A) (mostly deleted) locus, in addition to BRAF, help in the development of MSCs. Many driver genes, viz., cyclin-dependent kinase-4 (CDK4), neuroblastoma RAS viral oncogene homolog (N-ras), KIT proto-oncogene, receptor tyrosine kinase (KIT), mitogen-activated protein kinase 1/2 (MAPK1/2), Erb-b2 receptor tyrosine kinase 4 (ERBB4), glutamate receptor ionotropic 2A (GRIN2A), glutamate metabotropic receptor 3 (GRM3), Ras-related C3 botulinum toxin substrate 1 (RAC1), phosphatidylinositol 3, 4, 5-trisphosphate-dependent Rac exchanger 2 (PREX2), p53, and phosphatase and tensin homolog (PTEN), are implicated in the melanoma pathogenesis,[62] as shown in [Figure 2].
Diagnosis modalities available for skin cancer[63] have shown in [Figure 3]A. Clinically, the identification of MSCs is by the acronym “ ABCDE, ” which stands for asymmetry, border (irregular), color (dark or several), diameter (greater than 6 mm), and evolving (shape/size). The American Joint Committee on Cancer has proposed a TNM-based staging system, in which T describes the size of the tumor, also any spread of cancer into nearby tissue; N describes cancer spread to lymph nodes; and M describes metastasis or spread of cancer to other parts of the body. [Table 1] describes the TNM-based staging of MSCs. | Figure 3: (A): Diagnosis modalities for MSC. (B): Site-specific and systemic treatment modalities available
Click here to view |
The epidemiology of CM is more documented than NMSC. According to Ward et al.,[64] the incidence of MSC has increased by 4 –6% annually in fair-skinned people of North America, Northern Europe, Australia, and New Zealand. According to GLOBOCAN 2020, there were 324, 635 new cases and 57, 043 deaths due to MSC.[65] The mortality rate associated with MM is 90% and has a survival rate of fewer than 10 years when getting into metastasis.[66] In Europe, in 2000, 37, 000 deaths were caused by melanoma.[67] According to an estimate, 132, 000 new cases of melanoma occur worldwide each year. Caucasians are at a higher risk than African-Americans (10 times) and Hispanics (10 times). According to the World Health Organization (WHO), worldwide, approximately 65, 000 people die from malignant skin cancers annually.[68] CM represents less than 5% of all skin cancers in the USA, but causes most skin cancer deaths.[68] CM incidence rates across Europe have changed markedly during the past five decades. Recent analyses of European data have identified up to 10-fold increases in melanoma incidence in Scandinavian countries since the 1950s, with lesser but still considerable increases in western European nations.[69] CM mortality rates in the mid-1990s were highest in Nordic countries and lowest in southern European populations such as Greece, Spain, and Portugal.[69] The highest incidence rates of melanoma are reported from (essentially European migrant populations in) Australia and New Zealand (non-Maori population), with more annual incidence.
Early detection of melanomas can be “ cured ” by surgical excision alone. Nonetheless, MSC is fast to invade and metastasize, being the long-term survival poor for advanced disease.[70] Depending on whether cancer is confined (site-specific) or metastatic (systemic), there are several treatment choices for MSC, as shown in [Figure 3](B)]. Although site-specific treatments are effective, they have some limitations (aesthetic issues, pigmentary changes, atrophy, fibrosis, and cost burden). In addition, CM is still particularly problematic to treat once it has spread from its primary site.[2] Also, the treatment of MSC is expensive.[71]
Additionally, the treatments of MM have many adverse effects, which pose psychological burden and decrease the quality of life of the survivors. All this warrants the need of prevention, and management of this dreadful disease. Considering the easy accessibility, high tolerance as well as safety margins, and effective nature of herbal remedies, botanicals are gaining more popularity amongst scientists and public worldwide. In addition, Bandaranayake[72] reported that almost 80% of the world ’s population living rely upon herbal products as primary source of health. Hence, this seems to be an attractive strategy to delay/prevent skin carcinogenesis.[73]
Ayurveda is the traditional Indian system of medicine derived from ancient Vedic civilization (dating back to 5000 BC). Ayurveda aims to improve quality of life and longevity by healing the ill, maintaining health in the healthy, and preventing illness. Ayurveda plants have well-known beneficial effects such as antioxidant, anti-inflammatory, antiviral, antimicrobial, anti-ulcerative, antidiabetic, antigenotoxic, anticarcinogenic, and so on.[74] This review has selected potential Ayurveda herbs, viz., A. indica A. Juss (Nimba), O. tenuiflorum L. (Tulsi), P. emblica L. (Amalaki), S. album L. (Chandana), T. cordifolia (Willd.) Hook. F. and Thoms. (Guduchi), and W. somnifera L. Dunal (Ashwagandha), which are long being utilized in the Indian traditional system to tackle diverse health problems. These herbs can boost innate antioxidant responses within the skin and thus prevent melanoma skin carcinogenesis. The in-vitro and in-vivo reports presented in this review will help scientists discover novel drug discoveries and clinical trials with these magic herbs.
Moreover, this review will benefit the general public interested in alternative and traditional approaches to prevent or treat MSCs. Finally, we hope this review will further help expand the research and explore these herbs and many other potential herbs, which possess immense curative properties. The subsequent sections showcase the chemoprotective role of chosen Ayurveda herbs against MSCs.
Ayurveda for prevention of melanoma
The three basics of Ayurveda, which are very important for normal body function, are vata, pitta, and kapha (three basic humors of the body). Tridoshas is the condition in which all these three systems lose coordination and cause excessive cell proliferation.
In Ayurveda, cancer is represented either as “Granthi” (minor neoplasm) or as “Arbuda” (primary neoplasm, which is a significant, painful, immobile, deep-seated, and slow-growing tumor).[75] The stages of development of cancer in Ayurveda are (a) Sopha—swelling/inflammation; (b) Granthi— glandular swelling; (c) Arbuda—tumor; (d) Karkatarbuda—malignant tumor; (e) Adhyarbuda—metastasis in primary sites; (f) Dwirarbuda—distant metastasis; and (g) Vranarbuda—suppurating tumors. These stages also require other biofactors such as the Agni (digestive/metabolic factors), Srotas (body channels), and Dhatus (body organs) to achieve a disease. Ayurveda also believes that “Ama” (“incompletely digested,” a toxic, heavy, and sticky juice that originates as a waste product of digestion and metabolism) is the leading cause of several diseases, including cancer.[76] It is conjugated with Doshas or Dhatus and can circulate and interact with other excretory products to produce a reactive/toxic form, potentially disrupting the immune system and increasing the severity of the disease.
In Ayurveda, Kushta chikitsa deals with causes, types, symptoms, and treatment of skin diseases. According to Ayurveda, melanoma includes the violation of tridosha (Vata, Pitta, and Kapha). The main involvement of the skin is a disturbance of Pitta along with raktadosh (toxification of blood) effecting the Agni (digestive/metabolic factors), Sapta dhatu (body tissues), Satkriyakala (involvement of generic sequence), and Srotamsi (channels of the body). The main treatment that can be done is Jaloka Avacharana, known as leech therapy or bloodletting and it will help in removing toxins from the blood and, along with this herbal medicine, will help in stopping the melanoma from spreading.
Kushta roga is the broad term used in Ayurveda for various skin disorders, which are believed to be caused by vitiation of mostly pitta and rakta doshas. Melanoma is considered to be formed by vitiation of tridoshas and is known as kaaknak kushta (a subtype of maha kushta). The skin lesion has blackish/no fixed color in the middle and reddish at the periphery or vice versa and mostly asymmetrical.
Herbs are called “ Adaptogens” (in Ayurveda), which help the body cope with stress, and have immense potential to boost the body ’s antioxidant activity. Herbs can help in healing, as well as in combating the side effects and cancer-associated/chemotherapy-associated complications. Each herb contains multiple active components which act synergistically producing benefits and attenuates the adverse effects or toxicity. Thus, these days, it is crucial to raise awareness and encourage implementation of Ayurvedic therapies for combating cancer and use of integrated approach for tumor management.
Many Ayurveda herbs have played a significant role in treating different cancers. Instead of using targeted therapies for the destruction of the tumors, Ayurvedic herbs restore normal tissue functions (“Sama Dhatu Parampara”)[77] via boosting intrinsic antioxidant activity. Ayurveda herbs help reduce the side effects and cancer-associated complications. It is also helpful in post-surgery care.[78] These herbs improve the patient’s quality of life, who have no other choice. Therefore, herbs have been considered a robust chemopreventive strategy for skin cancer and developing skin cancer therapeutics. The present review summarizes some potential Ayurveda herbs (A. indica, O. tenuiflorum, P. emblica, S. album, T. cordifolia, and W. somnifera) in regulating oxidative stress, which can prevent skin cancer. It is crucial to raise awareness and to encourage the inclusion of these Ayurveda herbs in the daily routine for preventing skin cancer. [Figure 4] depicts the antioxidant mechanism of these Ayurveda herbs in skin cancer prevention. | Figure 4: Activation of ARE/EpRE pathway by potential Ayurvedic herbs to prevent oxidative stress-induced cellular damage in the skin
Click here to view |
Potential Ayurveda herbs for preventing melanoma
(a) A. indica A. Juss (Nimba)
A. indica, also known as “Nimba,” in Ayurveda is an evergreen tree that belongs to the Meliaceae family native to India, Burma, Pakistan, Bangladesh, and Nepal. Various parts of the neem plant cure illnesses such as blood disorders, eye diseases, persistent fever, malarial fever, leprosy, skin diseases, ulcers, and wounds in Ayurveda, Unani, and homoeopathy systems of medicine, and this “ divine tree ” is now used in western medicine to treat various metabolic disorders. Due to numerous alkaloids, flavonoids, glycosides, and amino acids, neem has antifungal, anthelmintic, antibacterial, antiviral, antidiabetic, contraceptive, and sedative effects.[79] Two bioactive neem compounds, nimbolide and azadirachtin, have been researched extensively and found to aid cancer management through antitumor and antioxidant activity.[80] According to the literature review, A. indica defends the skin from the harmful effect of UV rays, other chemical contaminants, skin infections, and wounds.[81],[82],[83] Furthermore, the vitamins and fatty acids found in neem help minimize wrinkles and fine lines on the skin and provide an anti-aging benefit. The antioxidant and anti-oncogenic ability of neem against MSC has been summarized in this article, as shown in [Table 2].
(b) O. tenuiflorum L. (Tulsi)
O. tenuiflorum, also famous as “Holy basil” or “Queen of Herbs,” is a member of the Labiatae family that originated in north-central India and now grown throughout eastern Asia, Africa, China, America, and other parts of the world. Tulsi has an important religious and social significance in Hinduism. Tulsi is known as “The Incomparable One,” “Mother Medicine of Nature,” and “Elixir of Immortality” in Ayurveda because of its medicinal and spiritual properties.[84] In Ayurveda, basil tackles various ailments such as anxiety, cough, asthma, diarrhea, malaria, fever, arthritis, eye diseases, urinary tract infections (UTIs), indigestion, vomiting, back pain, gastrointestinal disorders, skin diseases, and insect bites.[85]Tulsi is high in nutrients and other chemicals, including fatty acids, sitosterol, eugenol, methyl eugenol, anthocyanidins, carotene, ascorbic acid, vitamin K, certain levels of sugars, flavonoids, saponins, tannins, and triterpenoids. Some of the isolated active components of the O. tenuiflorum are eugenol, ursolic acid, linalool, and isoeugenol. Research has shown that eugenol, apigenin, and luteolin reduce the dermatoxic effects of xenobiotics and UV exposure. Traditionally, it was topically applied on the skin to treat acne and other infections.[86]Tulsi also protects the skin by avoiding blackheads and treating fungal infections and wounds.[87] This article summarizes Tulsi’s antioxidant and anti-oncogenic ability against MSCs, as shown in [Table 3]. | Table 2: Various in-vitro and in-vivo studies on the anticancer effects of A. indica
Click here to view |
 | Table 3: Various in-vitro and in-vivo studies on the anticancer effects of O. tenuiflorum
Click here to view |
(c) P. emblica L. (Amalaki)
P. emblica, or “Indian gooseberry” and ‘Amalaki’ in Ayurveda, belongs to the Euphorbiaceae family and is widely cultivated in Nepal, India, Sri Lanka, South-East Asia, and China.[88] It is also known as “the King of Rasayana.” In traditional Chinese and Indian Ayurveda systems, its fruit treats diarrhea, jaundice, inflammation of the lungs and eyes, asthma, bronchitis, hemorrhage, dysentery anemia, jaundice, and dyspepsia. “Chyvanaprash,” a popular preparation comprising Amla along with other herbs, is very useful in anemia, asthma, inflammations of the lungs, and eye diseases. Amla has an abundance of phenolics, tannins, flavonoids, vitamins, amino acids, minerals, and vitamin c. Amla also possesses various medicinal benefits such as antidiabetic, hypolipidemic, antibacterial, antioxidant, anti-ulcerogenic, hepatoprotective, gastroprotective, antimutagenic, and chemopreventive effects.[88]P. emblica lessens the UV-induced erythema and reduces free radicals, thus acting as an anti-aging agent.[89] Its roasted crushed seeds mixed with oil can be used to cure itches and scabies. Epidermis lightening retailers in Europe, the Middle East, and Asia use Amla to treat freckles and age spots.[90],[91],[92]Amla’s antioxidant and anti-oncogenic ability against MSCs has been summarized in this article, as shown in [Table 4]. | Table 4: Various in-vitro and in-vivo studies on the anticancer effects of P. emblica
Click here to view |
(d) S. album L. (Chandana)
S. album, also known as “ Royal Tree,” is a member of the Santalaceae genus, found in tropical Asia, Australia, the Pacific Islands, and Hawaii.[93] Sandalwood and agarwood are the most common and widely used incense among Chinese and Japanese people.[94] The Egyptians used its wood for embalming the deceased to venerate the god.[95] In Buddhism, sandalwoods are considered the Padma (lotus) group and attributed to the Bodhisattva Amitabha. Sandalwood is one of the most often used scents in incense offerings to the Buddha.[94] It is also used in many industries to make perfumes, soaps, detergents, cosmetics, and insect repellents. Its wood has a strong fragrance and is the world’s second most costly wood.[95] It was classified as “vulnerable” in 1997 according to the International Union for Conservation of Nature (IUCN).[95]S. album can also cure skin diseases such as pimples, scars, and eczema. Sandalwood essential oil, which is expensive in its pure form, is mainly used in Ayurvedic medicine to relieve anxiety. The essential oil derived from sandalwood is good for toning the skin and treating skin problems. It also has anti-aging and anti-tanning properties.[96],[97] Alpha-santalol, one of the active constituents of sandalwood oil, has been investigated extensively for its anticancer, anti-inflammatory, and antifungal properties.[98],[99] Sandalwood&# 8217;s antioxidant and anti-oncogenic ability against MSC has been summarized in this article, as shown in [Table 5]. | Table 5: Various in-vitro and in-vivo studies on the anticancer effects of S. album
Click here to view |
(e) T. cordifolia (Willd.) Miers (Guduchi)
T. cordifolia, or “Amrita” or ‘Guduchi’ in Ayurveda, also known as “heavenly elixir,” belongs to the Menispermaceae family and is abundant in South Asia, Indonesia, the Philippines, Bangladesh, Thailand, Myanmar, China, and Sri Lanka.[100] Due to its high therapeutic value and rejuvenating ability, Ayurvedic and Chinese systems have traditionally used T. cordifolia to treat fever, asthma, dysentery, leprosy, malnutrition, jaundice, skin diseases, and diabetes. Its watery extract, Indian quinine, is very effective in fever, indigestion, rheumatism, urinary diseases, dyspepsia, general debility, syphilis, skin diseases, bronchitis, spermatorrhea, and impotence.[101],[102],[103] It contains different constituents such as alkaloids (berberine, palmatine, tembetarine, isocolumbin), diterpenoid lactones, glycosides, hormones, sesquiterpenoid, phenolics, aliphatic compounds, and polysaccharides.[104] Pharmacological research revealed its antibacterial, antioxidant, anti-inflammatory, immunomodulatory, antistress, antispasmodic, chemoprotective, radioprotective, neuroprotective, and hypoglycemic effects.[105] It is the best remedy for skin problems such as black spots, pimples, fine lines, wrinkles, acne, and it also slows down the aging process.[106] The antioxidant and anti-oncogenic ability of Giloy against MSCs has been summarized in this article, as shown in [Table 6]. | Table 6: Various in-vitro and in-vivo studies on the anticancer effects of T. cordifolia
Click here to view |
(f) W. somnifera (L.) Dunal (Ashwagandha)
Ashwagandha, also known as “Indian ginseng,” belongs to the Solanaceae family in Ayurveda, is grown in India, Nepal, China, Baluchistan, Afghanistan, Sri Lanka, Congo, South Africa, Egypt, Morocco, Jordan, and Yemen.[107]W. somnifera is an Ayurvedic herb graded as a “Rasayana” (the most revered Ayurvedic herb). Its roots treat obstinate ulcers and rheumatic swelling, and its root decoction to pregnant and older adults is a nutrient and health restorative tonic. Its root is also helpful in alleviating inflammation, pain, constipation, and backache.[108],[109] In addition, its roots can serve as a nerve tonic, aphrodisiac, and sedative. Its powdered root is beneficial with equal parts of ghee and honey for impotence or seminal debility. Because of the presence of steroidal alkaloids and steroidal lactones, it has immunomodulatory, anti-inflammatory, anti-arthritis, antibacterial, antioxidant, antidiabetic, antitumor, and neuroprotective properties.[107] Several studies have showed the anticancer activity of W. somnifera against cancers of colon, prostate, blood, lung, breast, pancreas, kidney, head, and neck in humans,[110] whereas stomach and skin in mice.[111] Withaferin A and withanolide D, two main withanolides, are responsible for much of Ashwagandha’s pharmacological effects. However, few studies have advocated the clinical uses of W. somnifera to manage different cancers.[112]Ashwagandha also benefits the skin by replenishing natural oils and creating skin-enriching compounds such as hyaluronan, elastin, and collagen, giving the skin hydration, suppleness, and strength.[113],[114] Ashwagandha’s antioxidant and anti-oncogenic ability against MSC have been summarized in this article, as shown in [Table 7]. | Table 7: Various in-vitro and in-vivo studies on the anticancer effects of W. somnifera
Click here to view |
| Conclusion | | |
The literature survey revealed that these Ayurveda herbs contain numerous active components which prevent MSC by adopting unique mechanisms, as seen in [Figure 4]. Their beneficial effect is due to their ability to target multiple pathways in skin carcinogenesis, such as oxidative stress, inflammation, apoptosis, angiogenesis, and so on. However, there is a need for extensive research and clinical trials to investigate the antiskin cancer efficacy of these herbs in humans. Another loophole in the studies reported is the lack of pharmacokinetic profiles (absorption, distribution, metabolism, and excretion) of these herbs, which is crucial for further drug development. Nevertheless, exploring these herbs would be an inexpensive and straightforward way to improve health worldwide, supremely in developing countries.
In conclusion, these herbs showed a protective effect on MSC. A. indica showed chemoprevention via enhancing the immune system, decreasing the tumor growth, and decreasing the melanin production. O. tenuiflorum showed protective effects via increasing the apoptosis of tumor cells, decreasing the growth of tumors, and increasing the antioxidant potential. P. emblica showed protection via decreasing the modulation of extracellular matrix and decreasing the oxidative stress. S. album showed protection via decreasing the tumor growth, increasing the apoptosis of tumor cells, and cell-cycle arrest. T. cordifolia protected against skin cancer via decreasing angiogenesis and modulation in extracellular matrix. W. somnifera showed protection via decreasing tumor growth and increasing apoptosis of tumor cells. These herbs protect or reverse the damaging effects caused by UV radiation and other noxious environmental carcinogens. As these herbs are cost-effective and selectively cytotoxic, their individual use or combinatorial use will be more effective in preventing/treating MSC. However, these herbs warrant extensive investigations to obtain efficacious drugs in defeating melanoma skin carcinogenesis. This review draws scientists’ worldwide attention to exploring the Ayurveda medicinal system to discover new medicines. We believe that this approach could lead to new, less expensive, potentially successful anticancer drugs.
Acknowledgment
None.
Financial support and sponsorship
None.
Conflicts of interest
The authors have no potential conflicts of interest.
Authors’ contributions
SK, AA: Conceptualization, data curation, formal analysis, investigation, methodology; AA: roles/writing—original draft, writing; SK, AA: review and editing.
| References | | |
| 1. | Giacalone S, Spigariolo CB, Bortoluzzi P, Nazzaro G Oral nicotinamide: The role in skin cancer chemoprevention. Dermatol Ther 2021;34:e14892.  |
| 2. | D’Orazio J, Jarrett S, Amaro-Ortiz A, Scott T UV radiation and the skin. Int J Mol Sci 2013;14:12222-48. doi:10.3390/ijms140612222. |
| 3. | Elwood JM, Jopson J Melanoma and sun exposure: An overview of published studies. Int J Cancer 1997;73:198-203. |
| 4. | Lowe NJ An overview of ultraviolet radiation, sunscreens, and photo-induced dermatoses. Dermatol Clin 2006;24:9-17. doi:10.1016/j.det.2005.08.001. |
| 5. | Slominski A, Wortsman J Neuroendocrinology of the skin. Endocr Rev 2000;21:457-87. doi:10.1210/edrv.21.5.0410. |
| 6. | Fuchs E Scratching the surface of skin development. Nature 2007;445:834-42. |
| 7. | Slominski AT, Zmijewski MA, Skobowiat C, Zbytek B, Slominski RM, Steketee JD Sensing the environment: Regulation of local and global homeostasis by the skin neuroendocrine system. Adv Anat Embryol Cell Biol 2012;212:1-115. |
| 8. | Proksch E, Brandner JM, Jensen JM The skin: An indispensable barrier. Exp Dermatol 2008;17:1063-72. |
| 9. | Madison K Barrier function of the skin: “La Raison d’être” of the epidermis. J Invest Dermatol 2003;121:231-41. |
| 10. | Rogers HW, Weinstock MA, Harris AR, Hinckley MR, Feldman SR, Fleischer AB, et al. Incidence estimate of nonmelanoma skin cancer in the United States, 2006. Arch Dermatol 2010;46:283-7. doi:10.1001/ archdermatol.2010.19. |
| 11. | Geller AC, Annas GD Epidemiology of melanoma and nonmelanoma skin cancer. Semin Oncol Nurs 2003;19:2-11. |
| 12. | Gupta N, Gupta R, Acharya AK, Patthi B, Goud V, Reddy S, et al. Changing trends in oral cancer—A global scenario. Nepal J Epidemiol 2016;6:613-9. |
| 13. | Imanbayev K, Makishev A, Zhagiparov M, McLoone P Non-melanoma skin cancers at sites of previous frostbite: Case report and review. Case Rep Dermatol 2018;10:17-23. |
| 14. | Armstrong BK, Kricker A The epidemiology of UV induced skin cancer. J Photochem Photobiol B 2001;63:8-18. |
| 15. | Narayanan DL, Saladi RN, Fox JL Ultraviolet radiation and skin cancer. Int J Dermatol 2010;49:978-86. doi:10.1111/j.1365-4632.2010.04474.x. |
| 16. | Apalla Z, Nashan D, Weller RB, Castellsagué X Skin cancer: Epidemiology, disease burden, pathophysiology, diagnosis, and therapeutic approaches. Dermatol Ther (Heidelb) 2017;7:5-19. |
| 17. | Tan BL, Norhaizan ME Oxidative stress, diet and prostate cancer. World J Mens Health 2021;39:195-207. |
| 18. | Donaldson MR, Coldiron BM No end in sight: The skin cancer epidemic continues. Semin Cutan Med Surg 2011;30:3-5. doi:10.1016/ j.sder.2011.01.002. |
| 19. | World Health Organization. Ultraviolet Radiation and the INTERSUN Programme—Skin Cancers. World Health Organization; 2011. Available from: https://www.who.int/news-room/questionsand-answers/item/radiation-ultraviolet-(uv)-radiation-andskin-cancer. [Last accessed on 14 March 2016]. |
| 20. | De Gruijl FR Skin cancer and solar UV radiation. Eur J Cancer 1999;35:2003-9. |
| 21. | Rigel DS, Carucci JA Malignant melanoma: Prevention, early detection, and treatment in the 21 st century. CA Cancer J Clin 2000;50:215-36; quiz 237-40. |
| 22. | Rupani R, Chavez A Medicinal plants with traditional use: Ethnobotany in the indian subcontinent. Clin Dermatol 2018;36:306-9. |
| 23. | Eid A, Jaradat N, Elmarzugi N A review of chemical constituents and traditional usage of Neem plant ( Azadirachta indica). Palest Med Pharm J 2017;2:75-81. |
| 24. | Baral R, Chattopadhyay U Neem ( Azadirachta indica) leaf mediated immune activation causes prophylactic growth inhibition of murine Ehrlich carcinoma and B16 melanoma. Int Immunopharmacol 2004;4:355-66. |
| 25. | Roy MK, Kobori M, Takenaka M, Nakahara K, Shinmoto H, Isobe S, et al. Antiproliferative effect on human cancer cell lines after treatment with nimbolide extracted from an edible part of the neem tree ( Azadirachta indica). Phytother Res 2007; 21:245-50. |
| 26. | Akihisa T, Noto T, Takahashi A, Fujita Y, Banno N, Tokuda H, et al. Melanogenesis inhibitory, anti-inflammatory, and chemopreventive effects of limonoids from the seeds of Azadirachta indicia A. Juss. (neem). J Oleo Sci 2009;58:581-94. |
| 27. | Akihisa T, Kojima N, Katoh N, Kikuchi T, Fukatsu M, Shimizu N, et al. Triacylglycerol and triterpene ester composition of shea nuts from seven African countries. J Oleo Sci 2011;60:385-91. |
| 28. | Barik S, Bhuniya A, Banerjee S, Das A, Sarkar M, Paul T, et al. Neem leaf glycoprotein is superior than cisplatin and sunitinib malate in restricting melanoma growth by normalization of tumor microenvironment. Int Immunopharmacol 2013;17:42-9. |
| 29. | Banerjee S, Ghosh T, Barik S, Das A, Ghosh S, Bhuniya A, et al. Neem leaf glycoprotein prophylaxis transduces immune dependent stop signal for tumor angiogenic switch within tumor microenvironment. PLoS One 2014;9:e110040. |
| 30. | Jeon HJ, Kim K, Kim C, Kim MJ, Kim TO, Lee SE Molecular mechanisms of anti-melanogenic gedunin derived from neem tree ( Azadirachta indica) using B16F10 mouse melanoma cells and early-stage zebrafish. Plants 2021;10:330. https://doi.org/10.3390/plants10020330. |
| 31. | Birt DF, Pour PM, Nagel DL, Barnett T, Blackwood D, Duysen E Dietary energy restriction does not inhibit pancreatic carcinogenesis by N-nitrosobis-2-(oxopropyl)amine in the Syrian hamster. Carcinogenesis 1997;18:2107-11. |
| 32. | Van Dross RT, Hong X, Essengue S, Fischer SM, Pelling JC Modulation of UVB-induced and basal cyclooxygenase-2 (COX-2) expression by apigenin in mouse keratinocytes: Role of USF transcription factors. Mol Carcinog 2007;46:303-14. |
| 33. | Pisano M, Pagnan G, Loi M, Mura ME, Tilocca MG, Palmieri G, et al. Antiproliferative and pro-apoptotic activity of eugenol-related biphenyls on malignant melanoma cells. Mol Cancer 2007;6:8. |
| 34. | Byun S, Lee KW, Jung SK, Lee EJ, Hwang MK, Lim SH, et al. Luteolin inhibits protein kinase C (epsilon) and c-Src activities and UVB-induced skin cancer. Cancer Res 2010;70:2415-23. |
| 35. | Verschooten L, Smaers K, Van Kelst S, Proby C, Maes D, Declercq L, et al. The flavonoid luteolin increases the resistance of normal, but not malignant keratinocytes, against UVB-induced apoptosis. J Invest Dermatol 2010;130:2277-85. |
| 36. | Monga J, Sharma M, Tailor N, Ganesh N Antimelanoma and radioprotective activity of alcoholic aqueous extract of different species of Ocimum in C(57)BL mice. Pharm Biol 2011;49:428-36. |
| 37. | Wölfle U, Esser PR, Simon-Haarhaus B, Martin SF, Lademann J, Schempp CM UVB-induced DNA damage, generation of reactive oxygen species, and inflammation are effectively attenuated by the flavonoid luteolin in vitro and in vivo. Free Radic Biol Med 2011;50:1081-93. |
| 38. | Fujii T, Wakaizumi M, Ikami T, Saito M Amla ( Emblica officinalis Gaertn.) extract promotes procollagen production and inhibits matrix metalloproteinase-1 in human skin fibroblasts. J Ethnopharmacol 2008;119:53-7. |
| 39. | Majeed M, Bhat B, Anand TS Inhibition of UV induced adversaries by β-glucogallin from amla ( Emblica officinalis Gaertn.) fruits. Indian J Nat Prod Resour 2010;1:462-5. |
| 40. | Majeed M, Bhat B, Anand S, Sivakumar A, Paliwal P, Geetha KG Inhibition of UV-induced ROS and collagen damage by Phyllanthus emblica extract in normal human dermal fibroblasts. J Cosmet Sci 2011;62:49-56. |
| 41. | Fujii T, Okuda T, Yasui N, Wakaizumi M, Ikami T, Ikeda K Effects of amla extract and collagen peptide on UVB-induced photoaging in hairless mice. J Funct Foods 2013;5:451-9. https://doi.org/10.1016/j.jff.2012.11.018. |
| 42. | Birla N, Das PK Phytochemical and anticarcinogenic evaluation of Triphala powder extract, against melanoma cell line induced skin cancer in rats. Pharm Biol Eval 2016;3:366-70. |
| 43. | Dwivedi C, Zhang Y Sandalwood oil prevent skin tumour development in CD1 mice. Eur J Cancer Prev 1999;8:449-55. |
| 44. | Bommareddy A, Hora J, Cornish B, Dwivedi C Chemoprevention by alpha-santalol on UVB radiation-induced skin tumor development in mice. Anticancer Res 2007;27:2185-8. |
| 45. | Arasada BL, Bommareddy A, Zhang X, Bremmon K, Dwivedi C Effects of alpha-santalol on proapoptotic caspases and p53 expression in UVB irradiated mouse skin. Anticancer Res 2008;28:129-32. |
| 46. | Zhang X, Chen W, Guillermo R, Chandrasekher G, Kaushik RS, Young A, et al. Alpha-santalol, a chemopreventive agent against skin cancer, causes G2/M cell cycle arrest in both p53-mutated human epidermoid carcinoma A431 cells and p53 wild-type human melanoma UACC-62 cells. BMC Res Notes 2010;3:220. |
| 47. | Santha S, Dwivedi C Α-santalol, a skin cancer chemopreventive agent with potential to target various pathways involved in photocarcinogenesis. Photochem Photobiol 2013;89:919-26. |
| 48. | Dickinson SE, Olson ER, Levenson C, Janda J, Rusche JJ, Alberts DS, et al. A novel chemopreventive mechanism for a traditional medicine: East Indian sandalwood oil induces autophagy and cell death in proliferating keratinocytes. Arch Biochem Biophys 2014;558:143-52. |
| 49. | Leyon PV, Kuttan G Inhibitory effect of a polysaccharide from Tinospora cordifolia on experimental metastasis. J Ethnopharmacol 2004;90:233-7. |
| 50. | Leyon PV, Kuttan G Effect of Tinospora cordifolia on the cytokine profile of angiogenesis-induced animals. Int Immunopharmacol 2004;4:1569-75. |
| 51. | Devi PU, Kamath R, Rao BS Radiosensitization of a mouse melanoma by Withaferin A: In-vivo studies. Indian J Exp Biol 2000;38:432-7. |
| 52. | Mathur S, Kaur P, Sharma M, Katyal A, Singh B, Tiwari M, et al. The treatment of skin carcinoma, induced by UV B radiation, using 1-oxo-5β, 6β-epoxy-witha-2-enolide, isolated from the roots of Withania somnifera, in a rat model. Phytomed 2004;11:452-60. |
| 53. | Kalthur G, Mutalik S, Pathirissery UD Effect of withaferin A on the development and decay of thermotolerance in B16F1 melanoma: A preliminary study. Integr Cancer Ther 2009;8:93-7. |
| 54. | Kalthur G, Pathirissery UD Enhancement of the response of B16F1 melanoma to fractionated radiotherapy and prolongation of survival by withaferin A and/or hyperthermia. Integr Cancer Ther 2010;9:370-7. |
| 55. | Mayola E, Gallerne C, Esposti DD, Martel C, Pervaiz S, Larue L, et al. Withaferin A induces apoptosis in human melanoma cells through generation of reactive oxygen species and down-regulation of Bcl-2. Apoptosis 2011;16:1014-27. |
| 56. | Li W, Zhao Y Withaferin A suppresses tumor promoter 12-O-tetradecanoylphorbol 13-acetate-induced decreases in isocitrate dehydrogenase 1 activity and mitochondrial function in skin epidermal JB 6 cells. Cancer Sci 2013;104:143-8. |
| 57. | Halder B, Singh S, Thakur SS Correction: Withania somnifera root extract has potent cytotoxic effect against human malignant melanoma cells. PLoS One 2015;10:e0141053. |
| 58. | Maliyakkal N, Appadath Beeran A, Balaji SA, Udupa N, Ranganath Pai S, Rangarajan A Effects of Withania somnifera and Tinospora cordifolia extracts on the side population phenotype of human epithelial cancer cells: Toward targeting multidrug resistance in cancer. Integr Cancer Ther 2015;14:156-71. |
| 59. | Nagy Z, Cheung BB, Tsang W, Tan O, Herath M, Ciampa OC, et al. Withaferin A activates TRIM16 for its anti-cancer activity in melanoma. Sci Rep 2020;10:19724. |
| 60. | Das P, Deshmukh N, Badore N, Ghulaxe C, Patel P A review article on melanoma. J Pharm Sci Res 2016;8:112-7. |
| 61. | Gloster HM Jr, Neal K Skin cancer in skin of color. J Am Acad Dermatol 2006;55:741-60. doi:10.1016/j.jaad.2005.08.063. |
| 62. | Paluncic J, Kovacevic Z, Jansson PJ, Kalinowski D, Merlot AM, Huang ML, et al. Roads to melanoma: Key pathways and emerging players in melanoma progression and oncogenic signaling. Biochim Biophys Acta 2016;1863:770-84. |
| 63. | MacFarlane D, Shah K, Wysong A, Wortsman X, Humphreys TR The role of imaging in the management of patients with nonmelanoma skin cancer: Diagnostic modalities and applications. J Am Acad Dermatol 2017;76:579-88. |
| 64. | Ward WH, Lambreton F, Goel N, Jian QY, Farma JM Clinical Presentation and Staging of Melanoma. Exon Publications; 2017. p. 79-89. |
| 65. | Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: Cancer J Clin 2021;71:209-49. |
| 66. | Eggermont AM, Spatz A, Robert C Cutaneous melanoma. Lancet 2014;383:816-27. |
| 67. | Boyle P, Dore JF, Autier P, Ringborg U Cancer of the skin: A forgotten problem in Europe. Ann Oncol 2004;15:5-6. |
| 68. | American Academy of Dermatology. Skin Cancer—Stats and Facts. American Academy of Dermatology; 2011. Available from: https://www.aad.org/media/stats-skin-cancer. [Last accessed on 14 March 2016]. |
| 69. | Whiteman D, Green A Epidemiology of malignant melanoma. In: Dummer R, Pittelkow MR, Iwatsuki K, Green A, Elwan NM, editors. Skin Cancer—A Worldwide Perspective. Berlin, Heidelberg: Springer; 2011. |
| 70. | Sobanko JF Optimizing design and execution of linear reconstructions on the face. Dermatol Surg 2015;41(Suppl. 10): S216-28. |
| 71. | Gordon LG, Elliott TM, Olsen CM, Pandeya N, Whiteman DC Multiplicity of skin cancers in Queensland and their cost burden to government and patients. Aust N Z J Public Health 2018;42: 86-91. |
| 72. | Bandaranayake WM, editor. Modern phytomedicine. Turning Medicinal Plants into Drugs. Weinheim (Germany): Wiley-VCH; 2006. p. 25-57. |
| 73. | Barnes LE, Mazur C, McDaniel DH Cosmeceuticals using vitamin C and other antioxidants. In: Comstock J, Gold MH, eds. Cosmeceuticals. Vol. 5. Basel: Karger Publishers; 2021. p. 38-46. |
| 74. | Prasad S, Srivastava SK Oxidative stress and cancer: Antioxidative role of Ayurvedic plants. In: Cancer. 2nd ed. Oxidative stress and Dietary Antioxidants. Academic Press; 2021. p. 301-10. https://doi.org/10.1016/B978-0-12-819547-5.00027-4. |
| 75. | Kumari V, Kaushal K Clinical study of Sahadevi ( Vernonia cinerea Less.) kshara in perspective of granthi wsr cancer. J Herb Med Res 2020;5:1-8. |
| 76. | Dash MK, Joshi N, Gautam DN New insights of Ayurveda formulation Pushpadhanwa rasa as a palliative therapy to improve the quality of life in ovarian cancer: A review. J Ayurveda 2019;VIII:117-31. |
| 77. | Chauhan A, Semwal DK, Mishra SP, Semwal RB Ayurvedic concept of shatkriyakala: A traditional knowledge of cancer pathogenesis and therapy. J Integr Med 2017;15:88-94. |
| 78. | Ganguly S Ayurveda for cancer therapy. World J Pharm Res 2020;3:1476-9. |
| 79. | Uzzaman S Pharmacological activities of neem ( Azadirachta indica): A review. Int J Pharmacogn Life Sci 2020;1:38-41. |
| 80. | Nagini S, Nivetha R, Palrasu M, Mishra R Nimbolide, a neem limonoid, is a promising candidate for the anticancer drug arsenal. J Med Chem 2021;64:3560-77. |
| 81. | Javed A, Qazi JI Efficacy of Azadirachta indica and Solanum nigrum for skin regeneration in mice. Pakistan J Life Soc Sci 2016;14: 158-66. |
| 82. | Silva AC, Eugênio AN, Mariano SS, Poletti S, Gaspi FG, Bittencourt JV, et al. Topical application of Azadirachta indica improves epidermal wound healing in hyperglycemic rats. Comparat Clin Pathol 2021;30:461-72. |
| 83. | Rahmani A, Almatroudi A, Alrumaihi F, Khan A Pharmacological and therapeutic potential of neem ( Azadirachta indica). Pharmacogn Rev 2018;12:250-5. |
| 84. | Dhama K, Sharun K, Gugjoo MB, Tiwari R, Alagawany M, Iqbal Yatoo M, et al. A comprehensive review on chemical profile and pharmacological activities of Ocimum basilicum. Food Rev Int 2021;37:1-29. |
| 85. | Mohan L, Amberkar MV, Kumari M Ocimum sanctum Linn.(TULSI)—An overview. Int J Pharm Sci Rev Res 2011;7:51-3. |
| 86. | Marwat SK, Khan MS, Ghulam S, Anwar N, Mustafa G, Usman K Phytochemical constituents and pharmacological activities of sweet basil- Ocimum basilicum L. (Lamiaceae). Asian J Chem 2011;23:3773. |
| 87. | Mandal U, Mallick SK, Mahalik G Ethnomedicinal plants used for the treatment and healing of skin diseases in Odisha, India: A review. Shodh Sanchar Bull 2020;10:100-8. |
| 88. | Ahmad B, Hafeez N, Rauf A, Bashir S, Linfang H, Rehman MU, et al. Phyllanthus emblica: A comprehensive review of its therapeutic benefits. S Afr J Bot 2021;138:278-310. https://doi.org/10.1016/j.sajb.2020.12.028 |
| 89. | Xu MF, Jia OY, Wang SJ, Zhu Q A new bioactive diterpenoid from Pestalotiopsis adusta, an endophytic fungus from Clerodendrum canescens. Nat Prod Res 2016;30:2642-7. |
| 90. | Chaudhuri R, Lascu Z, Puccetti G Inhibitory effects of Phyllanthus emblica tannins on melanin synthesis. Cosmet Toilet 2007;122:73-81. |
| 91. | Wang YC, Haung XY, Chiu CC, Lin MY, Lin WH, Chang WT, et al. Inhibitions of melanogenesis via Phyllanthus emblica fruit extract powder in B16F10 cells. Food Biosci 2019;28:177-82. |
| 92. | Ahmad B, Hafeez N, Rauf A, Bashir S, Linfang H, Rehman MU, et al. Phyllanthus emblica: A comprehensive review of its therapeutic benefits. South Afr J Bot 2021;138:278-310. |
| 93. | Santha S, Dwivedi C Anticancer effects of sandalwood ( Santalum album). Anticanc Res 2015;35:3137-45. |
| 94. | Goswami NB, Tah J White sandal ( Santalum album L.), a precious medicinal and timber yielding plant: A short review. Plant Arch 2018;18:1048-56. |
| 95. | Kumar AA, Joshi G, Ram HM Sandalwood: History, uses, present status and the future. Curr Sci 2012;103:1408-16. http://www.jstor.org/stable/24089347. |
| 96. | Kumar R, Anjum N, Tripathi YC Phytochemistry and pharmacology of Santalum album L.: A review. World J Pharm Res 2015;4:1842-76. |
| 97. | Dulal SR, Taher MA, Sheikh H Sandalwood oil can be a miraculous tackle on skin aging, skin appearance and wrinkle skin—A review. World J Pharmaceut Med Res 2019;5:51-5. |
| 98. | Moy RL, Levenson C Sandalwood album oil as a botanical therapeutic in dermatology. J Clin Aesthet Dermatol 2017;10:34-9. |
| 99. | Bommareddy A, Brozena S, Steigerwalt J, Landis T, Hughes S, Mabry E, et al. Medicinal properties of alpha-santalol, a naturally occurring constituent of sandalwood oil: Review. Nat Prod Res 2019;33:527-43. |
| 100. | Upadhyay AK, Kumar K, Kumar A, Mishra HS Tinospora cordifolia (Willd.) Hook. F. and Thoms. (Guduchi)—Validation of the Ayurvedic pharmacology through experimental and clinical studies. Int J Ayurveda Res 2010;1:112-21. |
| 101. | Spelman K Traditional and clinical use of Tinospora cordifolia, Guduchi. Aust J Med Herb 2001;13:49-54. |
| 102. | Sinha K, Mishra NP, Singh J, Khanuja SPS Tinospora cordifolia (Guduchi), a reservoir plant for therapeutic applications: A review. Indian J Tradit Knowl 2004;3:257-70. |
| 103. | Tiwari P, Nayak P, Prusty SK, Sahu PK Phytochemistry and pharmacology of Tinospora cordifolia: A review. Syst Rev Pharma 2018;9:70-8. |
| 104. | Reddy NM, Reddy RN Tinospora cordifolia chemical constituents and medicinal properties: A review. Sch Acad J Pharm 2015;4: 364-9. |
| 105. | Kaur P, Robin , Makanjuola VO, Arora R, Singh B, Arora S Immunopotentiating significance of conventionally used plant adaptogens as modulators in biochemical and molecular signalling pathways in cell mediated processes. Biomed Pharmacother 2017;95:1815-29. |
| 106. | Yates CR, Bruno EJ, Yates MED Tinospora cordifolia: A review of its immunomodulatory properties. J Diet Suppl 2022;19:271-85. |
| 107. | Mandlik Ingawale DS, Namdeo AG Pharmacological evaluation of Ashwagandha highlighting its healthcare claims, safety, and toxicity aspects. J Diet Suppl 2021;18:183-226. |
| 108. | Umadevi M, Rajeswari R, Rahale CS, Selvavenkadesh S, Pushpa R, Kumar KS, et al. Traditional and medicinal uses of Withania somnifera. Pharm Innov 2012;1:102-10. |
| 109. | Paul S, Chakraborty S, Anand U, Dey S, Nandy S, Ghorai M, et al. Withania somnifera (L.) Dunal (Ashwagandha): A comprehensive review on ethnopharmacology, pharmacotherapeutics, biomedicinal and toxicological aspects. Biomed Pharmacother 2021;143:112175. |
| 110. | Nema R, Khare S, Jain P, Pradhan A Anticancer activity of Withania somnifera (leaves) flavonoids compound. Int J Pharm Sci Rev Res 2013;19:103-6. |
| 111. | Padmavathi B, Rath PC, Rao AR, Singh RP Roots of Withania somnifera inhibit forestomach and skin carcinogenesis in mice. Evid Based Complement Alternat Med 2005;2:99-105. |
| 112. | Saggam A, Tillu G, Dixit S, Chavan-Gautam P, Borse S, Joshi K, et al. Withania somnifera (L.) Dunal: A potential therapeutic adjuvant in cancer. J Ethnopharmacol 2020;255:112759. |
| 113. | Machiah DK, Girish KS, Gowda TV A glycoprotein from a folk medicinal plant, Withania somnifera, inhibits hyaluronidase activity of snake venoms. Comp Biochem Physiol C Toxicol Pharmacol 2006;143:158-61. |
| 114. | Dar NJ, Hamid A, Ahmad M Pharmacologic overview of Withania somnifera, the Indian ginseng. Cell Mol Life Sci 2015;72:4445-60. |
[Figure 1], [Figure 2], [Figure 3], [Figure 4]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7]
|
Search Pubmed for