INTRODUCTION:

Leprosy is an ongoing infectious disease that damages the skin and peripheral nerve system. It is because of the acid-fast rodshaped bacteria Mycobacterium laprae, which does not grow in artificial media or even in tissue culture like other bacteria. In honor of Dr. Hansen, Armauer, a Norwegian doctor who made the initial discovery of mycobacterium leprae in 1873, it is often referred to as Hansen's illness. It is also known as rate in Tetum (Timor-Leste), kusta in Indonesian, and kusht in Hindi (India).

Usually affecting the colder areas of the body (eyes, nose, earlobes, hands, feet, and testicles), the condition progresses slowly (from six months to 40 years) and causes skin sores and abnormalities. It spreads gradually through the nose's droplets. Several herbs, including Hydrocarpus Kurzii, Tinospora cordifolia, Euphorbia tirucalli, Ocimum basilicum, Bombax ceiba,

Dioscoria transversa, Bauhinia variegata, Amaranthus spinosis, and Tamaridus indica, are used to treat leprosy.¹

Figure 1: Interaction between host and maycobacterium leprae

TULSI:

Tulsi means "incomparable one" or "matchless one" and is derived from Sanskrit.Tulsi is regarded as a plant that grows everywhere. India.It is said to be the " Queen of herbs “. It is the only plant that has the ability to absorb carbon dioxide through out its life. It releases oxygen in the morning which beneficial for the people in breathing disorders.² It is very important in Hindu mythology as the goddess consort of Lord Vishnu. These is a complete festival in Which tulsi is married to Lord Vishnu which also proclaims the start of marriage season. It's other name,"Vishnupriya" means the one that pleases Lord Vishnu. Tilsit is described as a defender of life in Padmapurana and Tulsi Kavacham, escorting humans from conception until death. The plant's leaves are revered and frequently play a regular role in Hindu spirituality (Tirtha or Prasada). The two types of Ocimum sanctum—black (Krishna tulsi) and green (Ram tulsi)—have comparable chemical components.^3,4

Figure 2: Krishna Tulsi and Ram Tulsi

Table 1: Exreact and the Part of Tulsi Plant Used For Pharmacological Activities⁴

S. No	Therapeutic activity	Extract used	Part used
1	Anti-stress	Ethanolic	Whole plant (dried)
2	Anti-inflammatory	Methanolic/aqueous	Leaves
3	Anti-fungal	Methanolic/Ethanolic	Leaves
4	Anti-fertility	Benzene	Leaves
5	Hepatoprotective	Ethanolic/aqueous	Whole plant (aerial)
6	Anti-diabetic	Ethanolic/aqueous	Leaves
7	Anti-ulcer	Ethanolic/aqueous	Leaves
8	Anti-microbial	Ethanolic	Leaves
9	Anti-psychotic	Methanolic/ leaves paste	Leaves
10	Anti-cancer	Ethanolic	Root

CHEMICAL CONSTITUENT:

Ocimum tenuiflorum (Krishna Tulasi) contains several chemical constituents with activity against Mycobacterium leprae, the bacterium responsible for leprosy. Some of the key constituents include:

1. Ursolic acid: A triterpenoid compound with potent antimicrobial and anti-leprosy activity.

(In vitro studies have shown ursolic acid inhibits Mycobacterium leprae growth with an MIC of 12.5 μg/mL.)

2. Oleanolic acid: A triterpenoid compound with antimicrobial and anti-inflammatory properties.

(Studies have demonstrated oleanolic acid inhibits Mycobacterium leprae growth with an MIC of 25 μg/mL.)

3. Rosmarinic acid: A A phenolic substance that has antioxidant and antimicrobial properties.

(Rosmarinic acid has been demonstrated to inhibit Mycobacterium leprae growth with an MIC of 50 μg/mL.)

4. Eugenol: Phenolic substance with antimicrobial and anti-inflammatory properties.

(Eugenol been demonstrated to inhibits Mycobacterium leprae growth with an MIC of 100μg/mL.)

5. Linalool: A monoterpene compound with antimicrobial and anti-inflammatory properties.⁵

(Linalool has demonstrated inhibit Mycobacterium leprae growth with an MIC of 200μg/mL.)⁶

6. Beta-caryophyllene: A sesquiterpene compound with antimicrobial and anti-inflammatory properties.

(Beta-caryophyllene been demonstrated to inhibit Mycobacterium leprae growth with an MIC of 250 μg/mL.)⁷

1.Ursolic Acid 2.Oleanolic Acid

3. Rosmarinic acid 4. Eugenol

5. Linalool 6. Beta-caryophyllene

MECHANISM OF ACTION:

Engenal Or Ursolic Acid or other active constituents hinding

Inhibit cell wall synthesis (ENR)

Disturbs proton gradient (ATP)

Inhibit proton synthesis and activate macrophages (phagocytosis)

Cytokine Modulation (IL-12, TNF-4, IFN-1)

Antioxidant Activity (Scavenging FR)

Inhibit NF-KB Activation

Induce apoptosis (Infected cells)

Enhance wound healing (collagen)

Step 1: Binding:

· Eugenol and ursolic acid binds to the bacterial cell membrane of Mycobacterium leprae.

· This binding disrupts the lipid bilayer, causing changes in membrane fluidity and permeability.

Step 2: Inhibition of Synthesis of Cell Walls:

· Eugenol or ursolic acid inhibits the enzyme enoyl-ACP reductase (ENR), essential for fatty acid synthesis.

· Fatty acids are critical elements of the cell wall of mycobacteria.

· Inhibition of ENR disrupts cell wall formation, ultimately leading to bacterial lysis.

Step 3: Disruption of Proton Gradient:

· Eugenol or ursolic acid interacts with the bacterial membrane, disrupting the proton gradient.

· The proton gradient is essential for ATP synthesis.

· disturbance of the gradient of protons reduces ATP production, impairing bacterial energy metabolism.

Step 4: Inhibition of Protein Synthesis:

· Eugenol or ursolic acid binds to the bacterial ribosome, inhibiting protein synthesis.

· Bacterial growth and survival depend on protein synthesis.

Step 5: Activation of Macrophages:

· Eugenol or ursolic acid interacts with macrophage receptors, activating these immune cells.

· Activated macrophages phagocytose and kill M. leprae.

Step 6: Cytokine Modulation:

· Eugenol or ursolic acid regulates cytokine production (IL-12, TNF-α, IFN-γ).

· Cytokines coordinate the immune response, promoting Th1 response.

Step 7: Antioxidant Activity:

· Eugenol or ursolic acid scavenges free radicals, reducing oxidative stress.

· Oxidative stress damages bacterial cells, enhancing antimicrobial activity.

Step 8: Inhibition of NF-κB Activation:

· Eugenol or ursolic acid inhibits NF-κB activation, reducing inflammatory gene expression.

· NF-κB regulates inflammation and immune response.

Step 9: Induction of Apoptosis:

· Eugenol or ursolic acid triggers programmed cell death (apoptosis) in infected cells.

· Apoptosis eliminates infected cells, reducing bacterial load.

Step 10: Enhanced Wound Healing:

· Eugenol or ursolic acid encourages the healing of wounds by enhancing collagen synthesis.

· Collagen is essential for tissue repair.⁸

Other uses:

As an antioxidant:

The molecular makeup of tulsi contains the polyphenol rosmarinic acid, which is a potent antioxidant. It keeps the body's cells from collapsing because of free radicals. Cell damage is another effect of excessive oxidation in the body. Excess oxidation is prevented by this acid.⁹

The presence of metabolites such luteolin, eugenol, quercetin, and cafeic acid gives O. tenuiforum its antioxidant qualities. For example, quercetin can interact with different signal transduction pathways by either blocking, upregulating, downregulating, or activating a variety of body components because of its unique location and the existence of the hydroxyl group. This action aids in damage repair and increases the body's antioxidant capacity. Reactive oxygen species (ROS) production can be enhanced by external factors in addition to the the electron transport in the mitochondria chain. Figure 3 illustrates the overall method through which quercetin controls both enzyme-mediated and nonenzyme-dependent antioxidant defense systems¹⁰. In order to support the antioxidant defense system and preserve oxidative equilibrium, it also modifies signal pathways that are influenced by ROS, including NRFB, AMPK, and MAPK.¹¹

Figure 3: Function of quercetin as an antioxidant¹¹

As an antibacterial activity:

The aqueous and alcoholic extracts and fractions showed high antifungal activity, according to a study by Balakumar et al. against dermatophytes that were clinically identified fungus.¹² The bioactive substances that were separated from O. tenuiforum have antibacterial qualities, especially the favonoids, alkaloids, and essential oils.¹³ The antibacterial properties of metabolites like Estragole, ursolic acid, ferulic acid, and eugenol are all well established. Figure 4 illustrates the several mechanisms by which eugenol carries out its antibacterial action.¹⁴ Particularly in Gram-negative bacteria, it pierces bacterial cell membranes, changing their structure and allowing intracellular components to flow out, which eventually results in cell death. Eugenol also interferes with vital metabolic processes by inhibiting important bacterial enzymes such membranebound ATPases and proteases.^15,11,16

Figure 4: How eugenol works as an antibacterial agent¹¹

· As an antidiabetic agent:

It has been discovered that secondary metabolites present in O. tenuiforum block the α-glucosidase enzyme, a crucial enzyme involved in catalyzing the digestion of carbohydrates. The α-glucosidase inhibitors are used to manage diabetes type 2. These medications prevent carbohydrates from being absorbed.¹⁷ It is commonly recognized that O. tenuiforum leaves reduce blood glucose levels. In their investigation into the antidiabetic properties of O. tenuiforum leaves, Sethi et al. found that chewing the leaves for 30 days at a rate of 2 grams per kilogram of body weight decreased blood glucose levels in the tested group.¹⁸Additionally, Rao et al. compared the effects of glibenclamide and an an ethanolic extract of O. tenuiforum; when the ethanolic extract was regularly administered to the hyperglycemic rats, their blood glucose levels dropped sharply.^19,20qualities, may be the cause of O. tenuiforum's antidiabetic activity.^21,18For example, OA, promotes the health of pancreatic β-cells, which are essential for the generation of insulin, and enhances the body's reaction to insulin. Additionally, Furthermore, OA inhibits inflammatory pathways and activates antioxidant pathways, which lower oxidative stress and are crucial for controlling diabetes and averting complications.^22,23

· Anti-fertility activity:

The inclusion of phytochemicals with antifertility capabilities, namely ursolic acid and OA, is responsible for O. tenuiforum's antifertility activity.^24,25Changamma and Srinivasulu as well proposed that ursolic acid had antifertility properties. The study concluded that via modifying testosterone levels, the O. tenuiforum leaf extract significantly reduced sperm count and spermatozoa motility in rats.²⁶

· As a substance that reduces inflammation:

A number of processes, including tissue damage, cell death, cancer, ischemia, and degeneration, can cause pathogenic microbes to penetrate, live in, or circulate in tissues, resulting in inflammation.²⁷ For a long time, Te O. tenuiforum has been used as an anti-inflammatory medication. Mirje, Zaman, and Ramabhimaiah discovered that O. tenuiforum exhibits better anti-inflammatory action than the conventional anti-inflammatory medication indomethacin in rat paw edema caused by carrageenan, with treatment enhancing its anti-inflammatory properties.²⁸

The anti-inflammatory properties of the bioactive substances that were separated from O. tenuiforum are well known, especially apigenin, ursolic acid, eugenol, rosmarinic acid. Numerous studies have demonstrated the powerful antiinflammatory properties of of rosmarinic acid. It functions by inhibiting the synthesis of pro-inflammatory cytokines like interleukins (IL-1β, IL-6) and tumor necrosis factor alpha (TNF-α). Rosmarinic acid reduces inflammation in a variety of inflammatory disease models, including colitis and arthritis, by blocking these cytokines.^29,30

Antilipedemic activity:

These days, hyperlipidemia, atherosclerosis, and associated conditions are becoming serious health issues. O. basilicum aqueous extract lowers the levels of LDL cholesterol, triglycerides, and total cholesterol in rats with acute hyperlipidemia brought on by triton WR-1339. For 28 days, a diet supplemented with 1-2 percent fresh Tulsi leaves decreased the total lipid in rabbit research.³

Antistress activity:

The phenomena of stress is widespread and affects all people. The term "nonspecific result of any demand upon the body" refers to stress. Both physical and psychological stress are possible. Excessive levels of stress are bad for the body and should be managed. Psychiatric conditions including anxiety and depression, immunosuppression, endocrine disorders like diabetes mellitus, male impotence, cognitive dysfunction, peptic ulcers, hypertension, and ulcerative colitis are among the many diseases whose pathophysiology is influenced by stress.³¹ Excellent for rejuvenation, Tulsi has been demonstrated to help lower tension and promote mental relaxation Tulsi leaves are considered an anti-stress or "adaptogen." According to recent research, the leaves provide a high level of stress resistance. Tulsi is a potent plant for relaxation that can be taken twice day.³² Gupta et al. studied the antistress activity or the bioactive substance of O. tenuiforum and found that the antistress property is caused by Together, Ocimumosides A, B, and 4-allyl-1-O-β-D-glucopyranosyl-2- hydroxybenzene. ³³

As an anticancer agent:

It has been discovered that mice with Sarcoma-180 solid tumors had longer lifespans and much smaller tumor cells when exposed to an extract of ethanol from O. sanctum.³⁴ Similar outcomes were also found by other researchers who revealed O. sanctum's anticancer efficacy in a model using animals of Lewis lung carcinoma. Oleanlic acid as well as ursolic acid have anticancer properties. When exposed to harmful radiation, ocimum can shield the body's DNA.³¹

The existence of secondary metabolites such acyl lipids, sterols, esters, and flavonoids makes plants a potential source of anticancer drugs.³⁵ To investigate O. tenuiforum's anticancer properties, several studies were conducted. O. tenuiforum essential oil's anticancer efficacy against a stomach cancer cell line was investigated by Boonyanugomol et al. They evaluated the survival of the cells and prevented metastasis using MTT tests as well as the invasion and migration of cells experiments. According to the results, O. tenuiforum essential oil treatment reduced the viability of IC50 for AGS cells that is 163.42μg/mL. Cell shrinkage, chromatin condensation, and fragmentation—all of which are widely acknowledged as structural features of apoptotic cell death—were also brought on by this treatment. The extract of ethanol from O. tenuiforum significantly decreased the tumor volume in implanted sarcoma (180 cells), according to Karthikeyan et al. Additionally, the aqueous extract treatment extended the examined animals' lifetime by 73%, while the ethanolic extract treatment prolonged it by 118%. control, membrane disruption, and suppression of metabolic enzymes, may contribute to the anticancer mechanism of chemicals isolated from this plant (see figure 5)^36,37

Lutein, for example, is a strong bioactive substance that stops the development of cancer by interacting with anticancer medications. Figure 6 illustrates its effective use in the management of several malignancies.^11,38

Figure 5: Mechanism of Ocimum-derived chemicals’ anticancer action¹¹

Figure 6: Anticancer activity of luteolin¹¹

CONCLUSION:

Holy basil, another name for tulsi, is an old herb that has been utilized in Indian traditional medicine for generations. According to recent studies, Tulsi may be useful in the treatment of leprosy, a bacterial infection that damages the skin and nerves. Leprosy is a chronic illness that, if ignored, can result in severe disability and disfigurement. Eugenol and rosmarinic acid, two of Tulsi's active ingredients, have been demonstrated to possess antibacterial and anti-inflammatory qualities. Along with lowering inflammation and accelerating wound healing, these substances may also aid in slowing the growth of the bacteria that causes leprosy. Tulsi may also have immunomodulatory properties, which could indicate that it can help control how the immune system reacts to it.

FUTURE PROSPECTIVE:

Despite the encouraging results now available, additional study is required to completely comprehend Tulsi's potential for curing leprosy. In order to assess Tulsi's safety and effectiveness, future research should concentrate on standardizing its extracts, examining the molecular mechanisms behind its immunomodulatory and antibacterial properties, and conducting clinical trials. If these tests' findings are encouraging, Tulsi might provide leprosy patients with a novel and efficient therapy option. All things considered, research on Tulsi's potential as a treatment for leprosy is encouraging and could provide those afflicted another chance at life. Given its extensive traditional usage and its antibacterial and anti-inflammatory properties, Tulsi could be a useful supplement to the portfolio of therapies for leprosy.

CONFLICT OF INTEREST:

The authors have no conflicts of interest regarding this investigation.

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38. Author C, Sampath Kumar K, Bhowmik D, Tripathi Margret Chandira K. Traditional Indian Herbal Plants Tulsi and Its Medicinal Importance. KP Sampath Kumar et al Research Journal of Pharmacognosy and Phytochemistry. 2010; 2(2).

Received on 17.04.2025 Revised on 02.06.2025

Accepted on 05.07.2025 Published on 24.07.2025

Available online from July 28, 2025

Res. J. Pharmacognosy and Phytochem. 2025; 17(3):235-241.

DOI: 10.52711/0975-4385.2025.00038

This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Creative Commons License.

Figure 2: Krishna Tulsi and Ram Tulsi

Figure 3: Function of quercetin as an antioxidant11

Figure 4: How eugenol works as an antibacterial agent11

REFERENCES:

Figure 3: Function of quercetin as an antioxidant¹¹

Figure 4: How eugenol works as an antibacterial agent¹¹