Keywords

4.1 Introduction

Having an extensive use from prehistoric time, aromatic and medicinal plants have gained attention of researchers and scientists to cure aliments. Edible plants are accepted as a potent biochemists and major sources of phytomedicine since time immemorial (Ross and Kasum 2002; Narendhirakannan and Hannah 2013). Aromatic plants with medicinal potential are increasingly used in several aromatherapy, medicinal market, perfumery, food applications, and cosmetics (Awuchi 2019). The API of most of the drugs discovered these days are found to be isolated from plant source (Mehndiratta et al. 2011). The special attention has been given to essential oils along with herbal extract in scientific research due to their extraordinary potential in pharmacology, aromatic flavors, and extensive traditional practice. A survey of WHO revealed that more than 80% patients in India, Burma, and Bangladesh are treated by traditional system of medicine using crude drug. The holy basil “tulsi” is well known for its religious and spiritual holiness. It is regarded as queen of herbs and comes under the family Labiatae (Raseetha Vani et al. 2009; Naibaho et al. 2013). The Sanskrit meaning of tulsi is “Matchless” and is very specially treated in Hindu culture (Kayastha 2014). A great importance is given to tulsi in the traditional system of medicine such as Ayurveda, Unani, and Siddha (Vogel 1997; Khurana et al. 2016). The phytochemical potential of tulsi is also mentioned in Greek and Romanian system of medicine. It is believed to have originated in India although the geographical distribution of holy basil is tropical Asia, northern and eastern part of Africa, Taiwan, Hainan Island, and certain parts of China. Ocimum sanctum is a plant with multiple health benefits. Tulsi is one of the most important sources of medicine. The essential oil and secondary metabolite constituents of tulsi impart extensive pharmacological potential and are suggested to be used for treatment of diarrhea, malaria, ulcer, dysentery, skin diseases, bronchitis, bronchial asthma, eye infections, chronic fever (Prakash and Gupta 2005; Kousik and Baldev 2012; Harun-Al-Rashid et al. 2013), etc. In addition Ocimum sanctum also exhibits anticancer, anti-diabetic, antimicrobial, antifungal, adaptogenic, and diaphoretic properties (Kousik and Baldev 2012; Harun-Al-Rashid et al. 2013). This book chapter aimed to collect and compile detail data regarding traditional uses, major chemical constituents, pharmacological potentials, clinical study, and marketed formulation of tulsi.

4.1.1 Morphology

Ocimum sanctum is an erect, perennial herb with characteristic aroma and growing up to height of 30–60 cm (Fig. 4.1). It is commonly propagated through seeds (Pandey et al. 2014). The leaves of tulsi are up to 5 cm long and simple, branched, opposite, obtuse, elliptical, oblong with dentate margin. The small hairy structures are found from the root to stem (Pattanayak et al. 2010). The flowers are small and reddish purple in color presented in compact clusters on cylindrical spikes. Fruits are small and when ripe seeds appear reddish yellow in color. Leaves are light green to dark purple greenish in color (Singh et al. 1996).

Fig. 4.1
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(a) Tulsi plant, (b) flowers of tulsi, (c) tulsi leaf

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4.1.2 Taxonomic Classification

Kingdom: Plantae

Sub-kingdom: Tracheobionta

Super-division: Spermatophyta

Division: Magnoliophyta

Class: Magnoliopsida

Sub-class: Asteridae

Order: Lamiales

Family: Lamiaceae

Genus: Ocimum

Species: sanctum

Binomial name: Ocimum sanctum L

4.1.3 Cultivation

Ocimum sanctum is a vital aromatic and medicinal plant which yields several aroma chemicals. Tulsi have wide uses in pharmaceutical industry, perfumery, cosmetics industry, and indigenous systems of medicine. Cultivation of the tulsi pant needs a favorable environment and necessary soil condition to rise into aroma-rich plant (Varghese et al. 2014). The cultivation of Ocimum sanctum can be well explained through below mentioned sub-heading (Vidhani et al. 2016; Saran et al. 2017):

  1. (a)

    Soil Condition

    Though Ocimum sanctum thrives well on a wide range of soils, it is well cultivated in saline and alkaline to moderate acidic soils with rich loam and poor laterite. For better vegetative growth of plant, well-drained soils are preferred (Böhme and Pinker 2014).

  2. (b)

    Climate

    The better plant growth with high oil content has been found in high temperature and long days. Tulsi flourishes well under light rainfall and slightly humid conditions. Ocimum sanctum is moderately tolerant to frost and drought (Cohen 2014).

  3. (c)

    Propagation

    Tulsi is propagated through fresh seeds. There is chance of deterioration due to high cross-pollination, and over generations of seeds, fresh seeds from pedigree stock are selected for plantings (Pattnaik and Chand 1996; Mandal et al. 2000).

  4. (d)

    Land Preparation

    The land proposed for cultivation of tulsi is well plowed and brought to fine tilth plot of convenient sizes. The recommended fertilizers of 15 t/ha as basal dose and enough farm yard manure are mixed well in soil (Selvam et al. 2013; Smitha and Tripathy 2016).

  5. (e)

    Nursery

    After the well preparation of land for cultivation, elevated seed beds (15 × 4 × 9 ft. size) are thoroughly prepared. 10 kg/bed farm yard manure and 200–300 g seeds/hectare are sown for healthy seedlings (Adhikari et al. 2014; Mridha and Rahman 2015). After sowing of seeds, the seed beds are irrigated using sprinkler hose. The seeds develop buds in 8–12 days, but the seedlings are ready to transfer in another place after 6 weeks at 4–5 leaf stage. After 15–16 days, 2% urea is sprayed before transplantation which promotes the healthy seedling growth (Anbarasan et al. 2016).

  6. (f)

    Transplanting

    Transplantation of seedling is done at 4–5 leaf stage with enough spacing for proper respiration of plants (Anbarasan et al. 2016). To get batter and high herbage with quality yield, the seedlings are transplanted at a spacing of 40 × 40 cm or 50 × 30 cm or 40 × 50 cm. Irrigation is done immediately after transplantation (Smitha et al. 2019). The gap filling and replacement of poor basils are done before the second irrigation to get uniform basil stand (Chandelia and Sharma 2011).

  7. (g)

    Manure and Fertilizer Application

    It is necessary to frequently restore the soil level to previous condition to get high oil yield. It is necessary to apply farm yard manure at 10 t/ha before planting. Freshly prepared manure and compost prepared from human excreta and city waste are avoided (Singhal et al. 2011). The best fertilizer dose recommended for tulsi cultivation is 120 kg nitrogen (N) and 60 kg P2O5 and K2O per hectare, whereas 120 kg of nitrogen (N) and 105 kg each of P2O5 and K2O per hectare are required for saline and alkaline soils. 50 and 100 ppm concentration of cobalt and manganese is used as micronutrients (Vetal et al. 2013; Khan et al. 2014).

  8. (h)

    Irrigation

    The season and moisture content of soil determine the requirements of irrigation of tulsi (Tomar and Minhas 2004). One irrigation is done immediately after transplantation, and three irrigations per month are done during summer season, whereas irrigation is done as per necessity (Suthar and Saran 2020).

  9. (i)

    Weeding

    For proper growth of the plant, weeding is much more necessary. Weeds have to be removed to inhibit the competition with transplanted herb for nutrients. The first and second weeding is done after 1 month and 2 months after planting the herb. Hoeing and earthing up operation is done after the second weeding, and mulch should be used to inhibit the growth of weeds and to maintain soil moisture (Cohen 2014).

  10. (j)

    Pest Control

    Few pests and diseases affect tulsi. Thus insecticides and pesticides are used to get rid of such pests. 10,000 ppm concentration of Azadirachtin spray is used to control Cochlochila bullita and leaf rollers (Kamaraj et al. 2008; Shetty et al. 2008). Spraying wettable sulfur (4 g/L of water) and drenching Bavistin 1% prevent crops from Oidium spp.-, Rhizoctonia solani-, and Rhizoctonia bataticola-like diseases (Kamaraj et al. 2008).

  11. (k)

    Harvesting

    Harvesting of tulsi plant is done after 90–95 days of planting. The crop harvesting is recommended on bright sunny days at full bloom phase to achieve higher amount of essential oil. Tulsi is not supposed to be harvested while there was rain in the previous day (Zheljazkov et al. 2008b). To avoid contamination the herb should be cut at 15–20 cm above ground level, and the surfaces that touch with plant during and after harvest should be cleaned well. The next harvest is done at every 65–75-day interval (Zheljazkov et al. 2008a).

  12. (l)

    Expected Yield

    The expected yield of tulsi plant is found to be 5 tons per hectare after harvesting 2–3 times in a year. The whole plant contains about 0.1–0.23% of essential oil with yield of 10–23 kg per hectare (Zheljazkov et al. 2008a).

4.2 Phytochemistry of Tulsi

4.2.1 Chemical Constituents

Several medicinal uses of Ocimum sanctum have been discussed along a long year of human civilization. The wide variety of treatments using Ocimum sanctum was possible due to its complex chemical constituents. The leaves, stem, roots, inflorescence, and seeds of Ocimum sanctum were analyzed. Most components were found in all the plant parts but were in different concentrations. Several phytochemicals like tannins, saponins, phlobatannins, flavonoids, phenolics, terpenoids, glycosides, and steroids with other mineral and micronutrients were confirmed by different chemical tests of various solvent extracts (Singh and Chaudhuri 2018). The phytochemicals present in O. sanctum are enlisted in Table 4.1 and Fig. 4.2. Phenolic compounds are important secondary plant metabolites and show notable health benefits. These compounds play different physiological roles in plants; they are used as growth regulators and as important precursor molecules for the biosynthesis of other molecules such as lignin and suberin, which are produced as a defense against different biotic and abiotic stresses. Terpenes are major constituents of essential oil (Gupta et al. 2007; Mahajan et al. 2013). They are well known for organoleptic properties in various plants. They show many ecological roles, which include antimicrobial and allelopathic properties along with herbivorous preventive and pollinator attractant.

Table 4.1 Summary of different phytochemicals present in Ocimum sanctum
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Fig. 4.2
figure 2figure 2

The phytochemicals present in O. sanctum

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4.2.2 Essential Oil

Essential oils are secondary metabolites from plants and composed of mainly volatile terpenes and hydrocarbons. They have characteristic strong odor. The quality, quantity, and composition of essential oil in individual plant may vary due to the weather, soil contents, plant organ, age, and vegetative cycle stage (Pandey et al. 2014). O. sanctum produces a higher amount of essential oil. The volatile oil from leaves consists of eugenol (C10H12O2) and methyl eugenol (C11H14O2) as major contents and other constituents, namely, carvacrol (C10H14O), ursolic acid (C30H48O3), linalool (C10H18O), and limatrol (Table 4.2). The volatile oil from seed contains sitosterol (C29H50O) and fatty acids (Garg 2005; Salles Trevisan et al. 2006; Nerio et al. 2010).

Table 4.2 List of bio-active essential oil present in O. sanctum
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Besides the secondary metabolites, the study revealed the presence of vitamin C, calcium, and phosphorous along with other micronutrients.

4.3 Ethnobotanical/Traditional Uses

Ocimum sanctum known as tulsi belongs to the Laminaceae family, the and plant is very important because of their healing potentials. OS is medicinally important herb, and it was well known for its medicinal activity from ancient periods of time. OS has been well described for its therapeutics and medicinal activity in Ayurveda and explained as Dashemani Shwasaharni (anti-asthmatic) and anti-kaphic drug (Kaphaghna). In Hindu culture Ocimum sanctum L. is sacred, and our ancestors used medicinal plants in daily life in south Asia to treat various illnesses (Gupta et al. 2014). Tulsi is well known as “The incomparable One,” “Mother Medicine of the nature,” and “The Queen of the Herbs” and is respected as “elixir of life.” As tulsi is found to be rich in aromatic nervine essential oils, it is a great choice to sooth the nervous system and support our body’s ability to respond the stress. Different parts like leaves, flowers, stem, root, seeds, etc. of tulsi plant have been used by traditional experts as expectorants, pain reliever, antiasthmatic, antiemetic, diaphoretic, anti-diabetic, hypotensive, antistress, anticold, stomachic etc. (Pandey and Madhuri 2010). The contemporary preparations of this sacred plant are herbal tea, decoction of leaves, powder in dry form, and preparation of fresh leaves with honey or ghee. The traditional or ethnobotanical use of tulsi (Table 4.3) can be well summarized in points (Mallikarjuna et al. 2011; Bhattacharyya and Bishayee 2013; Kumar et al. 2013; Gupta et al. 2014):

  • It is applied on affected surface to reduce swelling and pain.

  • Tulsi is effective in various skin disorders. Traditionally people use its paste to treat rashes, insects’ bites, and itching. Tree or whole plant is used in ring worm infections and also leukoderma (Gupta et al. 2014).

  • Freshly prepared juice of OS is applied in nasya karma to get relief from headache and disease of the head and neck.

  • Leaf extract is used for cosmetic purpose to reduce scars, acne, and pimples.

  • It is used to treat indigestion, constipation, and intestinal parasite.

  • Dry and crush leaves of tulsi are very efficient to cure fever and lower respiratory tract problems.

  • Traditionally it is efficiently employed as cardiac tonic and blood purifier.

  • It has been used as mild aphrodisiac to treat impulsive ejaculation.

  • People use it as anti-diabetic, hepatoprotective, and hypolipidemic agent from very ancient time.

  • Fresh juice obtained after crushing the leaves of tulsi is widely used for myringitis (inflammation in internal ear).

  • The leaves of Ocimum sanctum have been widely used to stop bleeding, cure eye diseases, and heal wounds in ruminants.

Table 4.3 Illustrating ethnobotanical use of tulsi
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4.4 Pharmacological Potential

Several scientific studies have discovered plethora of pharmacological potential of tulsi extract (steam distilled, pet. Ether extract, benzene extract) on the various systems like cardiovascular system, immune system, CNS, gastric system, and urinary system (Joshi et al. 2013). Exploring the literatures and scientific researches, it is found that tulsi shows a unique pharmacological activity that promotes health and resilience. Tulsi was used as potent adaptogens from ancient time in India which helps to relieve from the stress and the promotion of homeostasis (Cohen 2014). After much more study, it is shown that tulsi undeniably possess many pharmacological potentials. Various study shows that OS has a unique combination of actions that include antimicrobial, mosquito repellent, anti-diarrhea, antioxidant, anti-cataract, chemoprevention, radioprotection, hepatoprotection, neuroprotection, cardioprotection, anti-diabetic, anti-hypercholesterolemia, anti-hypertensive, anti-carcinogenic, analgesic, anti-pyretic, anti-inflammatory, anti-allergic, immunomodulatory, central nervous system stress, memory enhancement, anti-asthmatic, anti-tussive, diaphoretic, anti-thyroid, antifertility, antiulcer, anti-emetic, anti-spasmodic, antiarthritic, anti-stress, anti-leukodermal, and anti-coagulant activities (Buddhadev et al. 2014; Chandra and Abad Farooq 2014; Hussain et al. 2017).

4.4.1 Stress Resilience

Ocimum sanctum has been documented for extensive stress resilience in modern medicinal and pharmacognostic researches and studies. It has been found that tulsi possesses a potent adaptogenic properties (Mahdi et al. 2003). Preclinical studies have shown that Ocimum sanctum avoids stress-induced ulcer in rats in comparison to antidepressant drugs. It was found that tulsi plant extract exhibits anti-stress activity in albino rats by improving SDH level (Singh et al. 2012c). The abovementioned pharmacological potentials help the mind to cope up with several variety of chemical, physical, infectious, and emotional stress to reestablish psychological as well as physiological functions. Chewing 12 leaves of tulsi twice a day helps a person to get efficient relief from stress (Jothie Richard et al. 2016).

4.4.2 Anti-diabetic Potential

Diabetes is a metabolic disorder where level of sugar is increased in blood either because pancreatic β-cells are unable to produce sufficient insulin or because the body system is unable to respond to the insulin produced by the body. Tulsi is reported as anti-diabetic in many researches and studies. It is found to be much more effective in diabetes mellitus. Consumption of aqueous decoction of whole plant lowers the blood sugar level (Patil et al. 2011a). The ethanolic extract of the OS is subjected to the perfused pancreases for insulin secretion. It is observed that ethanolic extract stimulates the physiological pathway of insulin secretions by assessing the three important enzymes, i.e., glucokinase (GK), hexokinase (HK), and phosphofructokinase (PFK), along with insulin-dependent and insulin-independent tissues from the brain and kidney (Rani and Khullar 2004). Similar study has been conducted and was found reports eliciting a significant drop in mean FBS level from 174.35 mg/dL to 114.50 mg/dL, PP2 BS from 247.31 mg/dL to 152.02 mg/dL, and HBA1C. Furthermore preclinical studies have reported that use of both aqueous and alcoholic extracts of OS showed significant decrease in the level of blood sugar and glycosylated hemoglobin. The anti-diabetic properties of tulsi reported by various studies concluded that treatment of AQOS (aqueous extracts of Ocimum sanctum L.) significantly lowered blood glucose level in DM rats; this concludes the fall in fasting blood sugar and HbA1C (Patil et al. 2011b; Grover et al. 2002).

4.4.3 Antifungal Activities

Mycosis is the common fungal infection caused by the inhalation of spores of fungi or contact of fungal colony with skin. Keeping the body clean and staying in the dry environmental condition will minimize the infection though there is need of fungicides (Pandey and Madhuri 2010). The spectroscopic analysis of Ocimum sanctum revealed the presence of higher composition of methyl chavicol and linalool which have good antifungal activity against Candida and can be applied in treatment of various fungal infections (Singh and Chaudhuri 2018). The synergetic effect of essential oil of tulsi extract with azole (ketoconazole and fluconazole) is reported for candiodosis. The combination of ethanolic extract of leaves of tulsi with Cassia alata has shown anti-Cryptococcus activity even at higher temperature and lower pH. The investigation of antifungal activity of tulsi against dermatopathic fungi by 38A NCCLS method showed 200 μg/mL as MIC (minimum inhibitory concentration) and MFC (minimum fungicidal concentration) (Garg 2005). Extract of Ocimum sanctum disturbs ergosterol biosynthesis and membrane integrity and acts as antifungal medicine (Balakumar et al. 2011).

4.4.4 Antihypertensive and Cardioprotective Activities

Cardioprotective activities of Ocimum sanctum are found greatly effective in myocardial necrosis induced by isoproterenol in Wistar rat through upgrade of endogenous antioxidants (Singh et al. 2012b). Protection against the adriamycin (ADR)-induced lipid peroxidation in heart and liver microsomes is achieved by the ursolic acid derived from Ocimum sanctum (Zehra et al. 2019). The OS has been noted for the significant forestallation of transient cerebral ischemia and long haul cerebral hypoperfusion. Basic unsaturated fat contents like linoleic and linoleic acids promote the production of PGE 1 and PGE 3 which restrain the arrangement of PGE 2. Thus Ocimum sanctum offers huge assurance against the treatment of hypertension and cardiac problems (Krishna et al. 2014).

4.4.5 Hepatoprotective Activity

Ocimum sanctum shows response to the hepatoprotective activity. The studies have revealed that OS progresses the metabolic breakdown, purging dangerous/toxic chemicals from blood promoting healthy liver work (Singh et al. 2012a). Aqueous extract of tulsi shows the synergistic effect with gentamycin to control the rise in serum creatinine and urea in blood (Pandey and Madhuri 2010). The hepatoprotective potential of tulsi is also noted for the hepatotoxicity by paracetamol in rat. Hydro-alcoholic extract of tulsi leaves on oral administration (200 mg/kg) shows remarkable protection against liver injury induced by paracetamol. It was achieved by significant drop of serum enzyme aspartate aminotransferase (AST), alkaline phosphatase (ALP), and alanine aminotransferase (ALT) (Cohen 2014). Marked reduction in fatty acid degeneration of liver was also seen in histopathological examination. Leaves and seeds of tulsi have been detailed for diuretic activity and diminishment of urinary uric acid in albino rabbits. The continuous administration of water extract (3 g/100 g) of tulsi leaves for 6 days orally was beneficial against CCL4-induced liver dysfunction in albino rats (Lahon and Das 2011).

4.4.6 Antioxidant Activity

The physiological process like generation of energy in mitochondria, cell development regulation, and detoxification of xenobiotic in the human body leads to the formation of reactive free radicals (Kelm et al. 2000). The stressful lifestyle and various environmental factors like pesticides, chemical pollutants, and UV radiations contribute to ROS overproduction which causes tissue damage leading to deterioration of health condition. The phytoconstituents and secondary metabolites have significant role in scavenging the free radicals. Antioxidants from the tulsi, especially polyphenolic compounds, effectively impede hydrolytic and oxidative enzyme, decrease blood glucose and lipid level, and enhance immunity; therefore flavonoids have attracted attention to different issues mainly oxidative stress (Aqil et al. 2006). Existence of hydroxyl groups and keto group in phytochemicals of OS imparts free radical scavenging property and produce antioxidant activity (Shetty et al. 2008). Various in vitro study and research have been done to access the antioxidant potential of tulsi extract. Remarkable results were obtained in scavenging DPPH radical, superoxide radicals, ABTS radical, hydroxyl radicals, and reduction of phosphomolybdate ion (Veeru et al. 2009).

4.4.7 Antifertility Activity

Ocimum sanctum has significant antifertility activity in animals. It has been noticed from phytoconstituents from leaves, ursolic acid. The impact has been attributed to its antiestrogenic impact in male and inhibitory impact on ovum implantation in females. The OS leaves extract on benzene and petroleum ether showed 60–80% of antifertility activity in female rat. The extract of Ocimum sanctum in male rats exhibited increase sperm count, motility, and also weight of testis (Pandey and Madhuri 2010; Pattanayak et al. 2010).

4.4.8 Antiarthritic Activity

The antiarthritic potential was assessed against various chemicals produced from joint inflammations in rodents. Due to mimicking human rheumatoid diseases, Freund’s complete adjuvant-induced arthritis in the rat is an extensively used model to perform preclinical studies. For evaluation of antiarthritic potential, rat was injected with adjuvants, and inflammation in paws and joint nodules within the ear and tail (delayed systemic response) was induced. For the management of induced arthritic disease, fixed oil of OS was given at dose of 3 mL/kg (ip), and notable edema inhibition was achieved comparable to aspirin (100 mg/kg, ip). A notable inhibition of inflammation and arthritic nodules was noticed (Awuchi 2019). Antiarthritic potential of OS was also studied on formaldehyde-induced arthritis in rats, and marked improvement in the arthritic condition was achieved as result on daily application of OS fixed oil for 10 days ip. The fixed oil diminished the aroused paws up to a great extent (Singh et al. 2012a). The sequential release of mediators in turpentine oil-induced arthritis and carrageenan-induced paw edema, i.e., serotonin and histamine in earlier, kin in middle, and prostaglandins in later phase, is well inhibited by the fixed oil constituents of OS. These abovementioned mediators are inhibited by OS, so it is natural that fixed oil could inhibit inflammatory reaction involving different inflammatory mediators. The conclusion from the above study suggests potentially useful antiarthritic activity of fixed oil from OS (Pattanayak et al. 2010).

4.4.9 Antiulcer Activity

Antiulcer potential of OS was appraised on animals with induced gastro-intestinal ulcer. Fixed oil of O. sanctum possesses significant antiulcer and anti-inflammatory activity through antagonistic effect on the several chemicals and mediators responsible for gastric ulceration (Kousik and Baldev 2012). The management of gastric ulceration induced by NSAIDs, ethanol, histamine, reserpine, serotonin, and stress is accomplished due to lipoxygenase inhibitory, histamine antagonist, and antisecretory effects of the fixed oil extracted from OS (Kelm et al. 2000; Pattanayak et al. 2010). Drug possessing anti-inflammatory and antiulcer activity having null ulcerogenic effect has great importance in this modern era of allopathic medicine. A well-illustrated flowchart signifying the cause and management of gastric ulcer explains the marked antiulcer activity of OS shown in Fig. 4.3 (Singh and Majumdar 1999).

Fig. 4.3
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Flowchart showing the antiulcer potential of tulsi

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4.4.10 Anthelmintic Activity

The essential oil from Ocimum sanctum has extensive anthelmintic property. In the Caenorhabditis elegans model when tested in vitro, eugenol showed an ED50 of 62.1 μg/mL. Several studies have revealed essential oil of OS as the putative anthelmintic principle (Kousik and Baldev 2012). Ursolic acid found in tulsi has more efficient anthelmintic potential as compared to albendazole. It was found that ursolic acid paralyzes and kills worms at great extent (Inbaneson et al. 2012).

4.4.11 Anti-inflammatory Activity

Anti-inflammatory potential of OS is appraised in rats via carrageenan-induced paw edema, and it was found that 3 mL/kg fixed oil of OS when administered intra-peritoneally inhibits edema due to true anti-inflammatory action not due to counter-irritant property (Singh et al. 1996). The anti-inflammatory effect of oil is found independent on pituitary adrenal axis when evaluated in adrenalactomized and nonadrenalactomized rats (Mondal et al. 2009). A significant inhibitory action on various mediators of inflammation like histamine, serotonin, bradykinin, and prostaglandins was ascertained when tested on inflammatory mediator-induced edema. Ocimum sanctum exhibits anti-inflammatory potential via inhibition of both COX and LOX pathways of arachidonic acid metabolism (Singh et al. 2007). The relative contribution of OS fixed oil toward COX inhibition and LOX inhibition and inhibitory effect of antihistamine in arachidonic acid-induced paw edema were evaluated (Singh et al. 2007). The fixed oil of OS shows an excellent edema inhibitory potency than indomethacin or caffeic acid, a potent COX and lipooxygenase inhibitor. Thus the above results highlight the potent anti-inflammatory activity of Ocimum sanctum (Singh and Chaudhuri 2018).

4.4.12 Analgesic Activity

Pain is a distressing feeling often marked as cardinal signs of inflammation. The analgesic potential of OS fixed oil was estimated by means of chemical and thermal induced pain model. These include acetic acid writhing test and formalin-induced paw licking test, the formalin-induced model as a chemical pain model while tail flick, tail clip, and tail immersion method as a thermal-induced pain model (Kaur 2014). For the thermal induced pain model, response time of rat to pull back its tail from hot water or a hot wire is noted in tail immersion or tail flick model, while in tail clip method, response time to extricate the clip was noted. The insufficient elevation of pain threshold of rat toward heat emphasizes the non-central action of OS fixed oil. Thus, to differentiate the central and peripheral analgesia potency of OS fixed oil, acetic acid-generated writhing response in rat was used. Ethyl acetate extract of OS exhibited extensive inhibition of writhing persuaded by acetic acid and formalin-induced paw licking in dose-dependent manner. Therefore analgesia activity of OS oil appears to be superficially facilitated and achieved by additive inhibitory effects of histamine, acetylcholine, and prostaglandin (Prakash and Gupta 2005; Pandey et al. 2014).

4.4.13 Antipyretic Activity

Prostaglandins (PGE) mediate pyrogenic fever; hence inhibition of prostaglandin synthesis results in the antipyretic action of drugs. Various anti-inflammatory drugs including NSAIDs are supposed to inhibit prostaglandin synthesis. The antipyretic power of the OS has been tested with typhoid, a paratyphoid vaccine A/B that used pyrexia in mice (Kelm et al. 2000). Intra-peritoneal administration of fixed oil of OS (3 mL/kg) reduced the pyretic response in rats as compared to aspirin. The fixed oil from Ocimum sanctum is moreover found to impede the synthesis of prostaglandin emphasizing its antipyretic potential (Balakumar et al. 2011; Kaur 2014).

4.4.14 Anticancer Activity

Extensive studies, experiments, and clinical studies prove that OS holds a prodigious potential not only as prevention but moreover within the treatment of a wide range of cancers and tumors in human. The chemoprotective and antitumor therapeutic efficacy can be elucidated by potential of enzyme to elucidate activity and signal transduction pathways modulating strength as well as antioxidant, antiproliferative, anti-invasive, immunomodulatory, antiangiogenic, and anti-metastatic properties of OS. It plays a pivotal role in treatment and prevention of cancer by altering the several carcinogen metabolizing enzymes like CYP450, CYB5, aryl hydrocarbon hydroxylase (Karthikeyan et al. 1999a), etc., antioxidant enzymes such as CAT and SOD, and GSH and GSH-related enzymes like GST and GSH-Px (Tables 4.4 and 4.5). Studies have revealed that extract of OS mediates a notable decrease in volume of tumor, tumor cell size, rise in body weight, and survival rate of mice having sarcoma-180 solid tumor when administered 200 mg/kg, po (Singh et al. 1996; Kelm et al. 2000).

Table 4.4 In vitro studies for anticancer potential of O. sanctum
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Table 4.5 In vivo studies for anticancer potential of O. sanctum
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4.4.15 Antiviral Activity

Viral infections are the major causes of devastations for human and animal health worldwide. Being an obligate intracellular parasite, any intervention will affect the cellular metabolism of the host; thus, developing an antiviral drug is a great challenge for mankind (Tang et al. 2012). This has diverted attention of the researchers and scientists to develop antiviral drug from the native traditional plant (Cohen 2014; Kaur 2014). Several studies have revealed the antiviral property of Ocimum sanctum. Evaluation of antiviral potential against orthomyxovirus and paramyxovirus has shown the significant viral infection inhibitory potential of tulsi (Mohan et al. 2011). The ethanolic extraction of the air part of tulsi contains details of the content of flavonoids and polyphenolic compounds; these are further described before having the same antimicrobial properties. In silico experiments of phytochemicals such as SARS-CoV-2 primary protease inhibitors suggest that flavonoids and polyphenolic chemicals of tulsi, especially luteolin-7-O-glucuronide and chlorogenic acid, can bind by combining the active residual Cys145 of the COVID-19 main protease and inhibiting the immune system (Mohapatra et al. 2020). OS extract has shown a preventive degree against coronavirus due to its potential to restrain replication of coronavirus bolstered with its immunomodulatory feature and angiotensin-converting enzyme (ACE) II inhibiting potency (Varshney et al. 2020).

Studies show chemicals from OS like methyl eugenol, oleanolic acid, and ursolic acid which have a strong binding effect on both spike glycoprotein and RNA polymerase of novel coronavirus. These compounds showed better binding energy than the positive control (STGYC and remdesivir) (Kumar 2020).

4.4.16 Antimicrobial Activity

Ocimum sanctum has been described for its antimicrobial potency against Gram-positive and Gram-negative bacteria. The results have shown that the essential oil and extract of leaves (aqueous, alcoholic, and chloroform) are equally effective against both strains of bacteria (Cohen 2014; Kaur 2014). Tulsi’s antibacterial activity was evaluated against bacteria responsible for tooth decay, i.e., Streptococcus mutans, and it was confirmed that mouthwash with tulsi is equally effective as 0.2% chlorhexidine and listerine (Prakash and Gupta 2005; Singhal et al. 2011). Flavonoid content of OS showed significant efficacy against UTI-causing bacterial strains, e.g., Escherichia coli, Proteus, Klebsiella pneumoniae (gram –ve), Staphylococcus aureus, and Staphylococcus cohnii (gram +ve) using disk diffusion method. Orientin and vicenin synergistically show significant inhibition on bacterial growth compared to individual inhibitory potential of flavonoids (Prasannabalaji et al. 2012).

4.5 Clinical Efficacy of Tulsi [Clinical Study]

Tulsi has been reported beneficial for several disorders and diseases. Despite of abundant availability and extensive antiquity of traditional use of Ocimum sanctum, comparatively limited human interventions study has been done on clinical efficacy (Grover et al. 2002; Ghorbani 2013). Plethora of bioactive secondary metabolite constituents of tulsi act alone or synergistically to inhibit the inflammatory ailments, and regular consumption of tulsi assists in normalizing numerous metabolic disorders. A summary and critically evaluated human clinical trials enhance and potentiate the tulsi’s efficacy against various metabolic disorders, viral infections, neurocognition, and immunomodulation (Gupta et al. 2014; Ahirwar et al. 2018) which are well illustrated via Tables 4.6 and 4.7.

Table 4.6 A summary and critically appraise human clinical trials of Ocimum sanctum
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Table 4.7 Completed and ongoing clinical trials
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4.6 Nutritional Value

In addition to secondary metabolites, O. sanctum also contains several components which are of great nutritional values (Pattanayak et al. 2010; Kaur 2014). The herb is very low in calories. Fresh basil leaf is prodigious source of vitamin A; it is found that 175% of daily required dose is fulfilled by intake of 100 g fresh basil leaf. Basil herb contains a weighty amount of minerals like potassium (K), manganese (Mn), copper (Cu), and magnesium (Mg). Basil leaves are extremely rich in iron. 100 g of fresh leaves contains 3.17 mg of iron. Various researches have revealed the following components which are of great nutritional values and represented in Table 4.8 (Kumar et al. 2010; Prasannabalaji et al. 2012).

Table 4.8 Nutritive value per 100 g (source: USDA National Nutrient data base)
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4.7 Conclusion

OS is widely cultivated from the beginning of human civilization for its medicinal importance and as an herbal tea. Ayurveda, Siddha, and Unani described medicinal properties of this plant in the traditional system of medicine. The herbal drug remains devoid of side effects, so researches on the herbal plant were increasing and scientific research showed OS has huge biological potential. Research showed OS has various secondary metabolite, vitamins, and minerals. These phytoconstituents elucidate various pharmacological effects. Tulsi has significant pharmacological potential and has been clinically proved for both its beneficial application and effectiveness. The various clinical trials are completed, and some are still going on to establish its efficacy for chronic disease. However, some marketed product is also available as nutraceutical products.