Curry leaf

Curry Leaf (Murraya koenigii): A Comprehensive Reference

1. Identity and Botanical Description

The curry leaf is botanically known as Murraya koenigii and belongs to the family Rutaceae. Murraya koenigii (L.) Spreng. (Family: Rutaceae) is usually known as "curry leaves." The tropical and subtropical regions of the world have large distributions of M. koenigii. Among the 14 global species belonging to the genus Murraya, only two — M. koenigii and M. paniculata — are found in India.

Murraya koenigii, commonly known as Curry, Kadi, Kari Patta, or Mitha Neem, is one such plant that is well-known in many nations, including India. It is a native of Sri Lanka and India and is a member of the Rutaceae family. The curry tree is native to India; today found almost everywhere in the Indian subcontinent excluding the high altitudes of the Himalayas. As Meethi neem, Murraya koenigii Linn (Rutaceae) is a fragrant, tiny tree or shrub that is primarily deciduous and grows up to 6 meters in height. It is planted up to 1500 meters above sea level for its fragrant leaves and is found all over India.

This plant has a short stem with a diameter of 15–40 cm, which is grayish or brown, and lush foliage. Its compound leaves are bipinnately arranged, showcasing 11–21 leaflets, each measuring 2–4 cm in length and 1–2 cm in width, emitting a distinctive aroma. The bisexual flowers are small, fragrant, and white, while the small egg-shaped fruits have a length of 1.4–1.6 cm and a diameter of 1–1.2 cm, turning purplish-black when ripe.

For centuries, this plant has been used in diverse forms and holds a place of pride in Indian Ayurvedic medicine, where it is known as "krishnanimba." According to Ayurveda, Murraya koenigii is also named as "Mahaanimba."

Common Names and Synonyms

• Common names include: Curry, Kadi, Kari Patta, and Mitha Neem.
• Murraya koenigii (L.) Spreng., commonly known as curry leaves or "Salam India," belongs to the genus Murraya and the Rutaceae family.
• Synonyms in the literature include Bergera koenigii L.

Plant Parts Used

The parts used are leaves, flowers, bark, stems, roots, and fruits. Different parts of M. koenigii, such as its leaves, root, bark, and fruit, are known to promote various biological activities. Aromatic bioactive constituents in the leaves of M. koenigii retain their flavor and other qualities even after drying. M. koenigii leaves are slightly bitter in taste, pungent in smell, and weakly acidic.

Common Preparations and Forms

Murraya koenigii has been traditionally used in Ayurvedic and other herbal systems for its medicinal properties, and it is available in various forms including fresh leaves, dried leaves, tincture, powder, essential oil, and capsules. The plant can be prepared as a tea by steeping dried leaves in hot water, or as a decoction by boiling the leaves for a longer period, while an infusion involves soaking the leaves in cold or warm water. Topical applications include using the powder or essential oil to treat skin conditions or as a poultice.

2. Traditional and Historical Use

Murraya koenigii, a plant belonging to the Rutaceae family, is widely distributed in Eastern Asia and its medicinal properties are well documented in Ayurveda, the traditional Indian system of medicine. M. koenigii has a wide range of medicinal uses in numerous traditional medical systems, such as Ayurveda, Siddha, and Unani. These include treating bronchial illnesses, piles, vomiting, skin ailments, and more. Different tribal communities make extensive use of the plant's varied parts.

Curry leaf is an essential leafy spice used in Asian cuisines for its distinct flavor. It has prominently been used as folk medicine in India and other Asian countries as an analgesic, astringent, antidysenteric, febrifuge, hypolipidemic, and hypoglycemic agent. It is a powerful antioxidant and used for improvement of vision. It has also been used to treat night-blindness, and for regulation of fertility. The green leaves are stated to be eaten raw for curing dysentery, and the infusion of the washed leaves stops vomiting.

Fresh leaves are considered to have numerous medicinal properties for various diseases, including piles, inflammation, itching, fresh cuts, dysentery, and edema. A combination of curry leaf and buttermilk is used traditionally to treat diseases such as amoebiasis, diabetes, and hepatitis.

In traditional medicine, curry leaf is utilized as a blood thinner, febrifuge, antiemetic, antidiarrheal, and dysentery treatment. Chutneys and curries can benefit from its stomachic, tonic, purifying, and savory properties.

The leaves, the bark, and the roots of Murraya koenigii can be used as a tonic for stomachic. Fresh leaves juice mixed with lime and sugar is used to treat morning sickness, and root juice consumption is said to give renal pain relief.

Together with South Indian immigrants, curry leaves reached Malaysia, South Africa, and Réunion island. Outside the Indian sphere of influence, they are rarely found.

3. Nutritional Composition

The fresh leaves are reported to have a high nutritional value and are extremely rich in antioxidant vitamins, minerals, carbazole alkaloids, polyphenols, tannins, and saponins.

Analysis of dried leaves indicated they contain very little moisture (5.86%), fat (2.43%), and protein (3.81%). The carbohydrate content was substantial (60.24 g/100 g), with moderate amounts of ash (9.68 g/100 g) and fibre (5.22 g/100 g). The content of vitamin A was very high (100,989 IU) though other vitamins (B, C, and E) were present in lower amounts in the dehydrated form. Mineral content showed the presence of calcium, magnesium, sodium, potassium, and zinc.

Phytochemical studies of the leaves, roots, seeds, and stem bark of M. koenigii have yielded many essential metabolites such as terpenoids, polyphenols, coumarins, alkaloids, flavonoids, carotenoids, vitamins, and nicotinic acid.

4. Key Constituents and Active Compounds

4.1 Carbazole Alkaloids

This plant is known to be the richest natural source of carbazole alkaloids. Carbazole alkaloids present in M. koenigii (L.) Spreng. are responsible for its multiple biological properties, such as anti-tumor, anti-mutagenic, anti-oxidative, and anti-inflammatory activities.

This plant is also high in carbazole alkaloids such as mahanimbine, murrayanine, murrayacine, girinimbine, isomurrayazoline, mahanine, koenine, koenigine, koenidine, and koenimbine. Previous reports have demonstrated that the leaves, roots, and bark of this plant are rich sources of carbazole alkaloids, which produce potent biological activities and pharmacological effects.

Bioassay-guided fractionation of the acetone extract of the fresh leaves of Murraya koenigii resulted in the isolation of three bioactive carbazole alkaloids: mahanimbine (1), murrayanol (2), and mahanine (3), as confirmed by NMR spectral data. Compound 2 (murrayanol) showed an IC₅₀ of 109 μg/mL against hPGHS-1 and an IC₅₀ of 218 μg/mL against hPGHS-2 in anti-inflammatory assays, while compound 1 (mahanimbine) displayed antioxidant activity at 33.1 μg/mL. All three compounds were mosquitocidal and antimicrobial and exhibited topoisomerase I and II inhibition activities.

The carbazole alkaloids include a carbazole scaffold, which is a favored scaffold that is significant in drug development. The carbazole alkaloid mahanine, purified from the curry leaves, exerted anticancer activity by acting as a proteasome inhibitor and displayed antihyperglycemic action.

4.2 Essential Oil Constituents

The volatile aromatic hydrocarbons of M. koenigii essential oil were identified using retention indices and mass fragment pattern analysis. A total of 34 aromatic volatile constituents were identified from the oil, where two sesquiterpene hydrocarbons, β-caryophyllene (19.50%) and α-humulene (15.24%), were present as the major volatile metabolites. Detailed analysis revealed that the 34 volatile constituents could be grouped into 12 oxygenated monoterpenes, 12 sesquiterpene hydrocarbons, nine oxygenated sesquiterpenes, and one oxygenated diterpene.

GC and GC-MS analyses of essential oils from ten Indian locations revealed ninety compounds, constituting 93.8–99.9% of the essential oils. The highest concentrations of α-pinene (55.7%) and β-pinene (10.6%) were found in the essential oil of wild plants. α-Pinene (13.5–35.7%) and/or β-phellandrene (14.7–50.2%) were the dominant essential oil constituents of seven locations. (E)-Caryophyllene (26.5%, 31.5%) and α-selinene (9.5%, 10.4%) were the principal essential oil components of two locations.

Monoterpenes, sesquiterpenes, aldehydes, and ketones are the major classes of aromatic compounds present in the curry leaf.

4.3 Flavonoids and Polyphenols

Curry leaf plants high in phenolic acids (especially gallic acid) and flavonoids (especially myricetin, epicatechin, and quercetin) also exhibited significant anticancer activity in research. Rutin, quercetin, kaempferol, and apigenin, present in leaf extracts of M. koenigii, showed dose-dependent inhibition of endogenous 26S proteasome activity in MDA-MB-231 cells.

4.4 Additional Phytochemicals

Previous studies reported that the chemical content of M. koenigii includes alkaloids, phenylpropanoids, alkanes, and sesquiterpenes. The β-sitosterol content of the leaves was estimated to be 0.43 mg/gram of dried powder.

5. Established Mechanisms of Action

5.1 Anti-inflammatory Mechanisms

Research evaluated the in vitro and in vivo efficacy of a hydroalcoholic extract of M. koenigii curry leaves rich in carbazole alkaloids against lipopolysaccharide (LPS)-induced inflammation in RAW 264.7 cells. The activity of inflammatory cytokines interleukin 1 beta (IL-1β), interleukin-6 (IL-6), tumor necrosis factor (TNF-α), and p65-NFκB was significantly reduced by the hydroalcoholic extract of M. koenigii. In addition, the hydroalcoholic extract of M. koenigii reduced the expression of nitrotyrosine (NT), myeloperoxidase (MPO), IL-1β, intercellular adhesion molecule 1 (ICAM-1), and cyclooxygenase (COX-2), and increased the expression of Nrf2.

Girinimbine, a carbazole alkaloid, has been found to have a good role in total leukocyte migration and results in an appreciable reduction in pro-inflammatory cytokine levels.

5.2 Antidiabetic Mechanisms

Studies have investigated the effect of mahanimbine (carbazole alkaloid from Murraya koenigii leaves) on blood glucose and serum lipid profiles in streptozotocin-induced diabetic rats. Diabetes was induced in adult male Wistar rats by intra-peritoneal injection of streptozotocin (45 mg/kg). Mahanimbine (50 and 100 mg/kg) was administered as a single dose per week to the diabetic rats for 30 days. In the diabetic rats, the elevated fasting blood sugar, triglycerides, low-density lipoprotein, and very-low-density lipoprotein levels were reduced and high-density lipoprotein level was increased by mahanimbine at doses of 50 and 100 mg/kg. In addition, mahanimbine showed appreciable alpha-amylase inhibitory effect and weak alpha-glucosidase inhibitory effects when compared with acarbose.

5.3 Antiobesity and Hypolipidemic Mechanisms

Possible mechanisms involved in hypolipidemic ability can be attributed to the phytochemicals, some of which can reduce the absorption of cholesterol in the intestines or accelerate the catabolism of fats. Others can inhibit the enzyme HMG CoA reductase. M. koenigii can also inhibit pancreatic lipase. Mahanimbine, the carbazole alkaloid isolated from Murraya koenigii leaves, reduces weight gain as well as plasma total cholesterol and triglyceride levels significantly in high-fat-diet (HFD)-fed obese Sprague-Dawley rats. The major carbazole alkaloid mahanimbine was shown to inhibit pancreatic lipase in vitro with an IC₅₀ value of 17.9 μM.

5.4 Neuroprotective Mechanisms

M. koenigii promotes neuroprotective potential against orofacial dyskinesia induced by reserpine. Additionally, it stabilizes the levels of protective antioxidant enzymes like superoxide dismutase (SOD), catalase (CAT), and GSH, and inhibits lipid peroxidation (LPO) in the forebrain regions of reserpine-treated animals. Furthermore, it has been shown to significantly inhibit reserpine-induced abnormalities in behavior.

The oral administration of the leaf aqueous extract (100, 200, 400 mg/kg body weight) to aluminum-treated rats was found to significantly restore antioxidant parameters (Catalase: CAT, Glutathione reduced: GSH, Lipid peroxidation: LPO), reversing them to normal through the neuroprotective properties of the extract. The protective effect of M. koenigii on oxidative stress was most likely due to carbazole alkaloids, polyphenols, and flavonoids, which are known to have antioxidant properties.

5.5 Hepatoprotective Mechanisms

M. koenigii extended hepatoprotective activity when crude aqueous extracts were investigated against ethanol-induced hepatotoxicity in experimental animals. M. koenigii was reported to extend a protective effect in liver impairments in chronic alcoholism and was proved to be effective in maintaining the enzymatic oxidant status. Water extracts of carbazole alkaloids and tannin of M. koenigii were explored for their hepatoprotective activity against ethanol-induced hepatotoxicity in a HepG2 cell line model. They exhibited excellent hepatoprotective activity, maintaining the enzymatic and non-enzymatic antioxidant level at a near normal value and also maintaining the integrity of the cells.

5.6 Anticancer Mechanisms

In the plant extracts, the carbazole alkaloid mahanine has been identified as the principal bioactive component among several other chemical constituents. Scientific evidence derived not only from in vitro cellular experiments but also from in vivo studies in various cancer models is accumulating for the pronounced anticancer effects of mahanine.

Isolated carbazole alkaloids showed significant antitumor activity against MCF-7, HeLa, and P388 cell lines. Mahanimbine and essential oil in particular showed potent antibacterial and cytotoxic effect with dose-dependent trends (≤5.0 μg/mL).

6. Scientific Evidence by Area of Use

6.1 Glycemic Control and Antidiabetic Activity

Animal and In Vitro Evidence (substantial): Murraya koenigii extract possesses the property to decrease blood cholesterol and blood glucose levels in diabetic ob/ob mice. Mice received daily intraperitoneal injections of 80 mg/kg curry leaf extract for 10 consecutive days. The extract significantly decreased blood cholesterol level from 277.6 ± 16.6 mg/dL (day 0) to 182.0 ± 15.3 mg/dL (day 10, p < 0.01 compared with the change in vehicle group). The extract also significantly decreased blood glucose level from 387.0 ± 15.6 mg/dL (day 0) to 214.0 ± 26.6 mg/dL (day 10, p < 0.01). In addition, body weight was reduced after extract treatment.

Human/Clinical Evidence (limited): One clinical study indicated a transient reduction in fasting and postprandial blood sugar levels in non-insulin-dependent diabetes mellitus patients provided with 12 g of M. koenigii leaves powder supplementation.

In a study involving thirty female diabetes patients divided into three groups, G1 and G2 treatment groups received oral dosages of 1000 mg/day and 2000 mg/day of Murraya koenigii powder daily for 60 days. At day 60, blood glucose was significantly decreased (p < 0.05). Additionally, reductions in blood pressure and BMI were noted. These findings support the therapeutic potential of Murraya koenigii as a dietary supplement for diabetes management.

Another study reported that curry leaf extract showed a significant (p < 0.05) reduction in fasting blood sugar, random blood sugar, and glycated hemoglobin in both treatment groups.

Evidence Characterization: Research on M. koenigii with regard to obesity and diabetes has ranged from studies on crude extracts to isolated compounds. However, some of the studies require further in-depth analysis and validation of obtained results. Human clinical evidence remains limited; most robust data come from animal models, and large, well-controlled randomized clinical trials in humans are lacking.

6.2 Lipid Profile and Cardiovascular Effects

Animal Evidence: Terpenoids, flavonoids, saponins, and phenols isolated from different parts of the plant have unique hypocholesterolemic and antidiabetic activities. Among commonly used alternative therapies, plant sterols present in M. koenigii may help to reduce cholesterol and triglyceride levels, in turn managing heart diseases. Experimental animal studies are proving the hypolipidemic ability of M. koenigii.

Mahanimbine possesses anti-hyperglycemic and anti-lipidemic effects, suggesting it has beneficial effects in the management of diabetes associated with abnormal lipid profile and related cardiovascular complications.

Cardioprotective: In a rat model, doxorubicin-induced cardiotoxicity caused significant reduction in reduced glutathione, glutathione reductase, glutathione peroxidase, total antioxidant capacity, superoxide dismutase, and catalase activity, and a significant increase in lipid peroxidation. Treatment with Murraya leaf extract showed a significant increase in all antioxidant parameters and a significant reduction in lipid peroxidation. A significant reduction in myeloperoxidase activity expressed the anti-inflammatory effect of Murraya leaf extract. The doxorubicin-treated group showed histological evidence of extensive myocardial damage, while the plant-treated group showed a preserved myocardium with a lesser degree of damage.

Evidence Characterization: Evidence for lipid-modifying and cardioprotective effects is primarily from experimental animal studies and in vitro models. No published large-scale human clinical trials specifically examining cardiovascular endpoints have been identified in the peer-reviewed literature.

6.3 Antioxidant Activity

Curry leaf with the highest total flavonoid and total phenolic contents also showed the highest antioxidant activity as indicated by FRAP and DPPH assays. Among the studied locations, plants which had high levels of phenolic acids (especially gallic acid) and flavonoids (especially myricetin, epicatechin, and quercetin) also exhibited significant anticancer activity. Thus, the quantitative and qualitative analyses of major individual flavonoids and phenolics could provide an explanation for the correlation between total phenolic content and antioxidant capacity in curry leaf extracts. A wide concentration range of flavonoids and phenolic acids in curry leaf extracts may be due to several factors including growing location, altitude, climate, and temperature.

The leaves have been reported to increase digestive secretions and relieve nausea, indigestion, and vomiting. All changes caused by cadmium in rat cardiac tissue were ameliorated when the rats were pre-treated with an aqueous extract of curry leaf. The studies indicated that the aqueous extract of curry leaf protects the rat cardiac tissue against cadmium-induced oxidative stress possibly through its antioxidant activity.

Evidence Characterization: Antioxidant activity is well established in cell-free, in vitro, and animal studies. Evidence in humans is limited and not yet formalized in clinical guidelines.

6.4 Anticancer Activity

A M. koenigii-derived carbazole alkaloid showed growth inhibitory activity in human hepatocellular carcinoma and lung cancer cells in vitro. Rutin, quercetin, kaempferol, and apigenin, present in leaf extracts of M. koenigii, showed dose-dependent inhibition of endogenous 26S proteasome activity in MDA-MB-231 cells. M. koenigii contains remarkable anticancer compounds, especially mahanine, which has been reported to show anticancer activity targeting different signaling pathways.

Three carbazole alkaloids and essential oil from the leaves of Murraya koenigii were examined for their effects on the growth of five antibiotic-resistant pathogenic bacteria and three tumor cell lines (MCF-7, P388, and HeLa). The structures of these carbazoles were identified as mahanine (1), mahanimbicine (2), and mahanimbine (3).

Evidence Characterization: Anticancer evidence for M. koenigii and its isolated alkaloids is exclusively from in vitro cell-line studies and animal models. No human clinical trials of anticancer efficacy have been identified. This area remains at the preclinical stage.

6.5 Neuroprotective Activity

Supplementation with M. koenigii leaf extracts has been reported in the management of a wide spectrum of neurodegenerative diseases, like Alzheimer's disease (AD), Parkinson's disease (PD), and others. M. koenigii promotes neuroprotective potential against orofacial dyskinesia induced by reserpine. Additionally, it stabilizes the levels of protective antioxidant enzymes like SOD, catalase (CAT), and GSH, and inhibits LPO in the forebrain regions of reserpine-treated animals. Furthermore, it has been shown to significantly inhibit reserpine-induced abnormalities in behavior.

Atypical protein homeostasis — misfolding, aggregations and accumulations, oxidative stress, inflammation, and apoptosis — are common features in most neurodegenerative diseases. To date, due to the complex etiology and pathogenesis of neurodegenerative diseases, no defined treatment is available. There has been increasing interest in plant extracts as potential alternative medicines, as the presence of various active components may exert synergistic and multi-pharmacological effects.

Evidence Characterization: Neuroprotective evidence derives entirely from in vitro and in vivo animal studies. No controlled human clinical data for neurodegenerative disease outcomes have been identified.

6.6 Hepatoprotective Activity

The aqueous leaf extract of Murraya koenigii has been shown to reduce lipid peroxidation and to decrease cellular damage, thereby protecting liver from ethanol-induced toxicity.

Evidence Characterization: Hepatoprotective effects are substantiated by in vitro cell-line work (HepG2 model) and animal experiments. Human clinical evidence is absent.

6.7 Antimicrobial Activity

These carbazole compounds exhibited potent inhibition against antibiotic-resistant bacteria such as Staphylococcus aureus (210P JTU), Pseudomonas aeruginosa (ATCC 25619), Klebsiella pneumoniae (SR1-TU), Escherichia coli (NI23 JTU), and Streptococcus pneumoniae (SR16677-PRSP) with significant minimum inhibition concentration (MIC) values (25.0–175.0 mg/mL) and minimum bactericidal concentrations (MBC) (100.0–500.0 μg/mL).

Evidence Characterization: Antimicrobial activity has been demonstrated primarily through in vitro testing. No human clinical trials of M. koenigii as an antimicrobial agent have been identified.

6.8 Anti-obesity Activity

These findings demonstrate the excellent pharmacological potential of mahanimbine to prevent obesity. Mahanimbine, the carbazole alkaloid isolated from Murraya koenigii leaves, reduces weight gain as well as plasma total cholesterol and triglyceride levels significantly in HFD-fed obese Sprague-Dawley rats.

Evidence Characterization: Anti-obesity evidence derives from animal studies (high-fat-diet rodent models). Human evidence is lacking.

6.9 Gastroprotective Activity

Leaves of curry plant are rich in antioxidants with prolific free radical scavenging activities. This led researchers to investigate the efficiency of the use of curry leaves in ameliorating piroxicam-induced gastric damage. Piroxicam was orally administered (30 mg per kg body weight) in male albino Wistar rats to generate gastric ulcers. These rats were orally fed with graded doses of aqueous extract of curry or Murraya koenigii leaves prior to piroxicam administration.

Evidence Characterization: Gastroprotective activity has been investigated in animal models. No published human clinical trials addressing ulcer or gastric outcomes have been identified.

7. Body Systems Associated with Curry Leaf

This plant exhibits a wide range of pharmacological activities, including anti-inflammatory and analgesic effects, antidiabetic properties, anticancer activity, antioxidant activity, wound healing, antipyretic effects, immunomodulation, hepatoprotective effects, antihelminthic properties, antimicrobial activity, antiulcer effects, antidiarrheal effects, antiobesity effects, neuroprotection, and antitrichomonal activity.

The curry leaves have well-established therapeutic potentials in experimental animals including hypoglycemic, hypolipidemic, nephroprotective, hepatoprotective, gastroprotective, cardioprotective, atherosclerotic, and cholesterol-lowering effects.

The primary body systems implicated by research, in descending order of evidence volume, are:

• Metabolic / Endocrine System: Blood glucose regulation, insulin sensitivity, lipid metabolism (most-studied area, substantial animal evidence and limited human evidence).
• Gastrointestinal System: Digestion, antiemetic and antidiarrheal activity, ulcer protection (animal and traditional evidence).
• Hepatic System: Protection against toxic liver injury (in vitro and animal evidence).
• Nervous System: Neuroprotection in models of Alzheimer's disease and Parkinson's disease (animal evidence only).
• Cardiovascular System: Lipid lowering, antioxidant cardioprotection (animal evidence).
• Immune System: Immunomodulatory and antimicrobial activity (in vitro and animal evidence).
• Integumentary System: Wound healing, anti-inflammatory activity at the skin level (in vitro and animal evidence).

8. Dosage Forms and Reported Study Dosages

Dosages reported in the peer-reviewed literature vary widely by preparation, extract type, and study purpose. The following are reported only as they appear in source studies and do not constitute clinical recommendations:

• 12 g of M. koenigii leaves powder supplementation was used in a clinical study of non-insulin-dependent diabetes mellitus patients, with a transient reduction in fasting and postprandial blood sugar levels reported.
• In a study involving thirty female diabetes patients, treatment groups received oral dosages of 1000 mg/day and 2000 mg/day of Murraya koenigii powder daily for 60 days.
• In a mouse study, animals received daily intraperitoneal injections of 80 mg/kg curry leaf extract for 10 consecutive days.
• Mahanimbine (50 and 100 mg/kg body weight) was administered as a single dose per week to streptozotocin-induced diabetic rats for 30 days in an antidiabetic investigation.
• The oral administration of the leaf aqueous extract at 100, 200, and 400 mg/kg body weight was studied in aluminum-treated rats for neuroprotective effects.
• No signs of mortality or morbidity were seen in either male or female rats fed the ethanolic extract of M. koenigii leaf (300 and 500 mg/kg) for 28 days. At higher doses (900 mg/kg), no mortality was observed but congestion, hemorrhage, and lymphocyte infiltration were recorded. The study concluded that safe consumption could be as high as 500 mg/kg dosage without inducing any structural damage to the organs.

9. Safety Considerations

9.1 General Safety Profile

Curry leaf is consumed by people as part of their diet in India and South-East Asian and some European countries, and it has no widely reported side effects. One study showed that curry leaf has no adverse effects, as evident from the unchanged blood parameters/constituents and normal histopathology of hepatic tissue in Murraya koenigii-fed rats.

9.2 Acute and Chronic Toxicity Data

Results of an acute toxicity study showed that no mortality was observed at the highest dose level. The acute toxicity studies of crude powder and methanol extract of curry leaves showed that they did not possess any toxic effect at the studied dose levels and are safe up to the dose level of 9000 mg/kg (in Swiss albino mice).

No mortality or toxicity signs were observed in another toxicological study of Malaysian curry leaf extract. For the methanolic extract, an LD₅₀ of 200 mg/kg/day was reported. In addition, mice fed with the mahanine-enriched fraction (MEF) at different doses (5000 mg/kg body weight single dose, 300–1500 mg/kg BW/day for 14 days, and 300 mg/kg BW for 180 days) did not exhibit significant toxicity, mortality, or behavioral changes.

According to in silico analysis, phytomolecules such as mahanine, mahanimbicine, mahanimbin, isolongifolene, rutin, kaempferol, and many more were found to be safe per the GHS classification of acute toxicity. These phytomolecules have predicted LD₅₀ values of more than 4000 mg/kg.

However, findings on chronic dosing require careful interpretation: Oral MKL doses of 50, 100, 200, and 400 mg/kg/day were administered for a duration of ten weeks in a chronic LD₅₀ study. Group (5) at 400 mg/kg/day showed 100% mortality within the first month of the study. Group (4) at 200 mg/kg/day showed 50% mortality with signs of toxicity for the other animals. One report stated that the LD₅₀ of M. koenigii leaf extract is 200 mg/kg/day, and the safest extract dose should not exceed 50 mg/kg/day.

Administration of ethanolic extract of Murraya koenigii leaves for 28 days increased hemoglobin level and decreased body weight, subcutaneous fat, and blood glucose level at medium and high dose groups. Murraya koenigii did not show any structural damage to major organs except lymphocyte infiltration at high doses.

9.3 Seed Toxicity

The small black, shiny berries are claimed to be edible, but their seeds are reported to be poisonous. This is a key distinction from the leaves, which have a centuries-long history of culinary use.

9.4 Evidence Limitations and Research Gaps

Most pharmacological activity studies are still limited to in vitro and in vivo screenings, with mechanisms of action, bioavailability, and pharmacokinetics not yet fully explored. Further studies should focus on the isolation of phytochemical compounds guided by bioassays, formulation, and drug delivery methods, serving as the basis for drug discovery.

Reviews emphasize the need for more research on the molecular basis of such activity in various cellular and animal models to validate the efficacy of M. koenigii and its derivatives as potent therapeutic agents.

Discrepancies in reported LD₅₀ values across studies reflect differences in the extraction solvent (aqueous, methanolic, ethanolic), the plant part used, the route of administration (oral vs. intraperitoneal), and the animal species tested. These factors make direct comparisons across studies difficult, and extrapolation of animal doses to human therapeutic ranges must be treated with caution.

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