Clerodendrum phlomidis

Clerodendrum phlomidis: A Comprehensive Reference

1. Identity, Taxonomy, and Botanical Description

Clerodendrum phlomidis is a species of flowering plant in the family Lamiaceae. The plant has been used in Ayurvedic medicine, and some Ayurvedic sources refer to it by the synonym Clerodendrum multiflorum. It is a large shrub native to the Indian subcontinent and Myanmar. Clerodendrum phlomidis Linn. f. belongs to the family Lamiaceae and is an important and well-known medicinal plant in Ayurveda and the Siddha system of medicine.

Clerodendrum is a genus of approximately 500 species in the family Lamiaceae and is widely distributed throughout the whole world. The genus was formerly placed in Verbenaceae; the genus Clerodendrum, which consists of flowering plants, was once classified as a member of the Verbenaceae family but was recently reclassified as a member of the Lamiaceae family.

Clerodendrum phlomidis has leaves that are ovate, opposite, deltoid, hairy from below, and wavy. The flowers are in small rounded terminal panicles and bloom from August to February. The flowers are white or pinkish and are very fragrant. It resembles a large shrub or small tree growing up to 9 metres in height. It is found with yellow bark and a brown-coloured woody aromatic root. It has simple, ovate, opposite, membranous, and irregularly toothed leaves. Flowers of this herb are small and white-coloured. Fruits are saucer-shaped calyxes that surround the base and turn black when ripened.

Common Names and Synonyms

• Sanskrit / Ayurvedic: Agnimantha (a name derived from agni, meaning "fire," and mantha, meaning "to shake," because its wood was traditionally rubbed together to produce fire in ancient times)
• Hindi / regional names: Arni (also rendered as Aranii)
• Taxonomic note: Agnimantha includes two main types — Laghu Agnimantha (Premna integrifolia) and Brihat Agnimantha (Clerodendrum phlomidis), both of which hold significance in modern and traditional medicine.

Natural Distribution and Common Forms

Clerodendrum phlomidis thrives in tropical climates, especially in semi-shaded, moist loamy soils found in central India (Madhya Pradesh, Maharashtra) and parts of Sri Lanka. Clerodendrum phlomidis is a small plant common in India and Sri Lanka. It is used in Indian and Chinese systems of medicine.

Plant parts used medicinally include roots, root bark, stems, leaves, and flowers. Traditionally, various parts of this plant — roots, stems, leaves, and flowers — are used in Indian and Chinese medicine to treat ailments such as inflammation (Shotha), diabetes (Prameha), fevers (Jwara), gonorrhoea (Upadamsha), and obesity (Sthaulya). Preparations encountered in the scientific literature include aqueous (water) extracts, alcoholic (ethanol/methanol) extracts, petroleum ether extracts, ethyl acetate extracts, chloroform extracts, and decoctions, as well as incorporation into multi-herb Ayurvedic formulations.

2. Traditional and Historical Use

Ayurveda (India)

Agnimantha is a very important medicinal plant mentioned in texts since the Vedic period. This herb is considered the best Vatahara and Shothahara according to Acharya Charak, referring to its classical categorisation as a pacifier of Vata dosha and a reducer of oedema/inflammation. Clerodendrum phlomidis, known as Agnimantha in Ayurveda and belonging to the Lamiaceae family, is a crucial ingredient in the Ayurvedic formulation Dashamoola, a blend of ten roots that enhances vitality and promotes overall health.

The five trees of Dashamoola are Aegle marmelos (L.) Correa, Clerodendrum phlomidis L.f., Oroxylum indicum (L.) Kurz, Stereospermum chelonoides (L.f.) DC., and Gmelina arborea Roxb. Dashamoola is prepared by mixing equal parts of these roots. It is regarded as balancing all three doshas (Vata, Pitta, and Kapha) and is accordingly known as Tridosha Nashak.

Agnimantha is notably used in ancient Ayurvedic formulations such as Dashamoolarishta and Brihat Panchamoola Taila. The plant's roots and root bark are also the active component in Dashamoolarishta, a fermented liquid preparation. The activity of Clerodendrum phlomidis (CP) has been compared with aspirin and Dashamoolarishta (a multi-ingredient plant formulation containing Clerodendrum phlomidis), which have served as positive controls in pharmacological studies.

Clerodendrum phlomidis Linn. has been traditionally used for treatment of gynecological disturbances and for agricultural uses, and has been used in many Ayurvedic polyherbal formulations as an immunomodulatory agent.

Siddha and Unani Traditions

Clerodendrum phlomidis L. (Lamiaceae) is a shrub generally found in South-East Asia. This genus has great ethno-medicinal importance in various indigenous systems of medicine, including Indian, Chinese, Thai, Korean, Siddha, Unani, and Japanese traditions, for the treatment of numerous diseases.

Scope of Traditional Uses Across Cultures

Species within the genus Clerodendrum have been historically used as folk and traditional medicine to treat many kinds of diseases, such as cold, hyperpyrexia, asthma, furunculosis, hypertension, rheumatism, dysentery, mammitis, toothache, anorexia, leucoderma, leprosy, arthrophlogosis, and other inflammatory diseases in various parts of the world such as India, China, Korea, and others.

The pulp obtained from the crushing of the leaves is applied externally on swelling. The leaves of the plant are used for rheumatism and anti-microbial activities. Roots, stems, and flowers are used to treat various disorders in the Indian traditional system and folk medicine.

3. Key Constituents and Phytochemistry

More than eleven species of the Clerodendrum genus have been very well studied for their chemical constituents and biological activities, with 283 compounds identified, including monoterpene and its derivatives, sesquiterpene, diterpenoids, triterpenoids, flavonoid and flavonoid glycosides, phenylethanoid glycosides, steroids and steroid glycosides, cyclohexylethanoids, anthraquinones, cyanogenic glycosides, and others.

Phytochemical investigations specific to C. phlomidis have identified numerous individual compounds:

Flavonoids and Flavonoid Glycosides

It has been reported that pectolinaringenin, scutellarein, clerodin, clerodendrin, clerosterol, 24β-ethylcholesta-5,22E,25-triene-3β-ol, lup-20(29)-en-3-triacontanoate, 4,2′,4′-trihydroxy-6′-methoxychalcone-4,4′α-D-diglucoside, 7-hydroxyflavone, 7-hydroxyflavanone-7-O-glucoside, and α-L-rhamnopyranosyl-(1–2)α-D-glucopyranosyl-7-O-naringin-4′-O-α-D-glucopyranoside-5-methyl ether had been isolated from this plant.

Phytochemical investigation of C. phlomidis Linn. F. (Lamiaceae) has led to the isolation of two new flavonoid glycosides together with six known compounds identified as pectolinaringenin (3), pectolinaringenin-7-O-β-D-glucopyranoside (4), 24β-ethylcholesta-5,22E,25-triene-3β-ol (5), 24β-ethylcholesta-5,22E,25-triene-3β-O-β-D-glucopyranoside (6), (2S,3S,4R,10E)-2-[(2′R)-2′-hydroxytetracosanoylamino]-10-octadecene-1,3,4-triol (7), and andrographolide (8), identified mainly by spectroscopic analysis.

The ethanol extract of Clerodendrum phlomidis has shown positive results for tannins, flavonoids, anthraquinones, saponins, and glycosides. Non-polar solvent extracts of Clerodendrum phlomidis leaf have been analysed for their phytochemical components and identified by GC–MS analysis. More than 40 phytoconstituents were identified, with the major components found to be terpenoids, flavonoids, phytol, hexadecanoic acid, and palmitic acid.

Phenylethanoid Glycosides

Bioguided fractionation of active root extracts led to the isolation of a new phenylethanoid glycoside, β-(4-hydroxyphenyl)-ethyl-O-α-L-rhamnopyranosyl(1→3)-β-D-(4-O-2′,6′-dihydroxycinnamoyl)-glucopyranoside (designated phlomidoside, compound 10), along with 12 known compounds. Phlomidoside is a compound first characterised from C. phlomidis roots.

Marker Compounds for Quality Standardisation

To ensure identity and quality of the plant material and considering the wide therapeutic applications of L-DOPA, lupeol, and β-sitosterol, a study planned to quantify these marker constituents by TLC method found that the amounts of L-DOPA, lupeol, and β-sitosterol quantified from the leaves of C. phlomidis were 0.06806, 0.01733, and 0.06324 % w/w, respectively.

Phytochemical analysis has also revealed the presence of flavonoids, alkaloids, phenolic compounds, tannins, terpenoids, glycosides, saponins, carbohydrates, amino acids, and proteins.

Terpenoids

Terpenes, including monoterpene and its derivatives, sesquiterpene, diterpenoids, and triterpenoids, represent the major characteristic constituents with significant biological activities and have great potential to be developed into new drugs, especially for anti-inflammatory, antioxidant, anticancer, and antimicrobial purposes.

Pectolinaringenin: A Signature Flavone

The compound pectolinaringenin has been previously reported in Clerodendrum phlomidis (Seth et al., 1982) and is regarded as a key reference standard for the species. It has served as the standardisation reference compound in HPLC analysis of ethanol extracts.

4. Mechanisms of Action

Anti-inflammatory Mechanisms

Research on the isolated compound 3-hydroxy, 2-methoxy sodium butanoate (HMSB) from C. phlomidis leaves has been particularly informative. Prakash et al. reported that the monomer compound HMSB (at doses of 25, 50, 100 mg/kg) isolated from the leaves of C. phlomidis displayed anti-inflammatory and anti-arthritic effects in carrageenan-induced inflammation and Freund's complete adjuvant (FCA)-induced arthritic rat models. The results showed that HMSB could significantly reduce the paw oedema response, decrease lysosomal enzymes, protein-bound carbohydrates, and acute phase protein levels. In addition, HMSB could significantly down-regulate pro-inflammatory cytokines TNF, IL-1, and IL-6 protein levels and mRNA expression in the joints in a dose-dependent manner.

The levels of lysosomal enzymes and protein-bound carbohydrates were significantly decreased in ethanol extract-treated arthritic groups compared with the arthritic control. The pro-inflammatory cytokine levels were significantly decreased in a dose-dependent manner in all the Clerodendrum phlomidis-treated groups. Lysosomal membrane stabilisation is one proposed mechanism: when lysosomal membranes are stabilised, the release of destructive hydrolytic enzymes into inflamed tissue is attenuated.

Anti-obesity / Lipase Inhibition

The methanolic extract of C. phlomidis showed more promising anti-obesity effects than the alcoholic extract, possibly because of its multiple mechanisms. Anti-obesity activity produced by the methanolic extract is attributed to inhibition of pancreatic lipase activity, which delays the intestinal absorption of dietary fat.

Hypoglycaemic Mechanisms

The hydroalcoholic extract was found to be effective at stimulating the pancreatic β cells to secrete insulin after a glucose load, which helps maintain a normal blood glucose level.

Antiasthmatic / Bronchial Mechanisms

Histamine-induced contraction in isolated goat tracheal chain showed that the aqueous extract of Clerodendrum phlomidis inhibited the contractile effect of histamine (P < 0.05). A dose-dependent relaxation of goat tracheal chain was observed.

Central Nervous System Effects

The methanolic extract of Clerodendrum phlomidis Linn. (MECP) leaves was evaluated for psychopharmacological activities in several experimental models using Swiss albino mice and Wistar albino rats. MECP was found to cause significant reduction in spontaneous activity and decreases in exploratory behavioural profiles by the Y-maze and head dip test. It also showed reduction in muscle relaxant activity by rotarod, 30° inclined screen, and traction tests, as well as significantly potentiated the phenobarbitone sodium-induced sleeping time at doses of 200, 400, and 600 mg/kg body weight. These findings suggest CNS depressant/sedative properties.

Anti-fibrotic and Antioxidant (Pulmonary)

The ethyl acetate extract of C. phlomidis (CPEA) restored antioxidant enzyme levels and exerted anti-fibrotic and anti-inflammatory effects in rats with idiopathic lung fibrosis induced by bleomycin. CPEAs were shown to protect against lipopolysaccharide (LPS)-induced inflammation in vitro and bleomycin-induced idiopathic pulmonary fibrosis (IPF) in vivo.

5. Scientific Evidence by Area of Use

Overview: There are coincidences between some of the traditional usages of this plant and experimentally observed effects of the extracts, but very few biological studies are available on bioactive fractions and/or pure compounds. The entirety of the available scientific evidence derives from in vitro studies and preclinical (animal) investigations; no peer-reviewed, controlled human clinical trials specific to Clerodendrum phlomidis as a stand-alone intervention are indexed in the biomedical literature at the time of writing. The evidence base must therefore be considered preliminary.

5.1 Inflammation and Arthritis

Ethnopharmacological relevance: Clerodendrum phlomidis L.f. is used to treat several inflammatory diseases and arthritis in the Indian traditional system and folk medicine.

The most thoroughly studied pharmacological activity for C. phlomidis is its anti-inflammatory and antiarthritic action. The aim of one study was to evaluate the scientific basis of anti-inflammatory activity of different organic solvent extracts of Clerodendrum phlomidis and to evaluate the active crude extract for its anti-arthritic activity in a Freund's complete adjuvant (FCA)-induced animal model. The anti-inflammatory activity was studied using carrageenan and cotton pellet-induced inflammatory models. For anti-arthritic activity, the active crude ethanol extract was administered at concentrations of 100, 200, and 400 mg/kg body weight. The ethanol extract at 100, 200, and 400 mg/kg showed maximum inhibition of carrageenan-induced inflammation of 47.73%, 54.00%, and 65.15%, respectively. In the cotton pellet-induced granuloma model, the ethanol extract at different concentrations showed significant reduction in granuloma weight. In FCA-induced arthritis, the ethanol extract showed a significant reduction in paw thickness (100 mg/kg — 51.71%; 200 mg/kg — 57.58%; 400 mg/kg — 62.48%).

A separate study isolated the active principle. The compound 3-hydroxy, 2-methoxy sodium butanoate isolated from plant leaves displays considerable potency in anti-inflammatory action and has a prominent anti-arthritic effect. This was the first report of this natural compound with bioactivity.

Anti-inflammatory activity was also demonstrated with the aqueous root bark extract. CP in the dose of 21.6 ml/kg showed significant anti-inflammatory activity (15.85% inhibition in the carrageenan model and 50.38% inhibition in the model of chronic inflammation). In the peritonitis model, the maximum anti-inflammatory activity was 27.32% inhibition at the corresponding dose in mice. This study demonstrated anti-inflammatory activity of the aqueous extract of root bark and also provided a scientific basis for the inclusion of CP in the Dashamoolarishta formulation.

In the carrageenan-induced paw oedema model using the aerial parts, doses of 200 and 400 mg/kg caused significant inhibition of paw oedema of 34.02% and 26.80%, respectively, 4 hours after carrageenan administration. The chloroform extract of Clerodendrum phlomidis exhibited significant anti-inflammatory effect in albino rats. Results at both doses were also comparable with the standard drug phenylbutazone.

Evidence grade: Multiple independent preclinical (animal) studies with consistent findings support anti-inflammatory and antiarthritic effects. All evidence is from animal models. No human clinical data are available.

5.2 Diabetes / Hypoglycaemia

The plant exhibited a dose-dependent hypoglycaemic effect with maximum activity observed at 120 mg/kg b.w./p.o. The result of the alloxan-induced diabetic model depicted a significant decrease in blood glucose levels at different time intervals compared to the positive control group. The hydroalcoholic extract was found to be effective at stimulating the pancreatic β cells to secrete insulin after a glucose load, which maintained a normal blood glucose level.

A more recent investigation examined C. phlomidis leaf extract alongside another plant. The leaves of Clerodendrum phlomidis L. have been reported to exhibit antidiabetic, hypolipidaemic, and glucose-regulating effects. The study evaluated the phytochemical profile and insulin secretion, lipid regulation, and glucose-linked metabolic enzymes over 28 days of ethanolic test extracts. A 28-day chronic antidiabetic study was conducted in streptozotocin-induced male Wistar rats, with test groups receiving ethanolic extracts (100, 200, 400 mg/kg) and a standard group receiving glibenclamide (2.5 mg/kg).

Subacute toxicity studies (500–2000 mg/kg) confirmed that the ethanolic leaf extracts of C. phlomidis are non-toxic and harmless at 100, 200, and 500 mg/kg, exhibiting notable antidiabetic activity evidenced by improved glycaemic control and enhanced restoration of endocrine pancreatic islets. The plant extracts also demonstrated anti-Alzheimer's activity, as evidenced by cognitive assessment tools including the Morris Water Maze and Y-Maze.

Evidence grade: Preliminary; animal studies only. No controlled human trials have been published.

5.3 Respiratory / Antiasthmatic Effects

Roots and leaf extracts of Clerodendrum phlomidis have been used for the treatment of rheumatism, asthma, and diarrhoea, and possess sedative, antihypertensive, antidiabetic, and anti-obesity properties.

Mechanistic evidence for antiasthmatic action was generated using an in vitro smooth muscle preparation. A study was designed to evaluate the antiasthmatic activity of the aqueous extract of Clerodendron phlomidis on in vitro and in vivo animal models. Histamine-induced contraction in isolated goat tracheal chain showed that the aqueous extract inhibited the contractile effect of histamine (P < 0.05).

In a 2024 preclinical study, the ethyl acetate extract of C. phlomidis was shown to protect against LPS-induced inflammation in vitro and bleomycin-induced idiopathic pulmonary fibrosis (IPF) in vivo. The findings indicate that the extract demonstrates therapeutic potential for IPF in human subjects, as evidenced by its capacity to enhance antioxidant, anti-inflammatory, and anti-fibrotic markers in preclinical disease models. The authors explicitly stated that clinical trials are necessary, as the study indicated that the dietary flavonoid-rich component of the extract possesses anti-inflammatory and antioxidant properties.

Evidence grade: Preliminary in vitro and animal data only. The researchers themselves call for clinical trials.

5.4 Anti-obesity Effects

Anti-obesity activity of alcoholic and methanolic extracts of roots of Clerodendrum phlomidis was evaluated against high-fat diet-induced obesity in C57BL/6J female mice. Obesity was induced by feeding a high-fat diet for 13 weeks. The studies showed that the methanolic extract of C. phlomidis at 200 and 400 mg/kg significantly decreased food consumption, body weight, adiposity index, pancreatic lipase activity, adiposity diameter, glucose, insulin, SGOT, SGPT, triglycerides, total cholesterol, and LDL-c levels in mice with high-fat diet-induced obesity.

Evidence grade: Preclinical animal data only. No human trials have been conducted.

5.5 Antimicrobial and Antitubercular Effects

Hexane and ethyl acetate extracts of Clerodendrum phlomidis roots show antitubercular activity. Bioguided fractionation of active extracts led to the isolation of a new phenylethanoid glycoside (phlomidoside) along with 12 known compounds. Antitubercular activity of extracts and isolated compounds was determined by BACTEC radiometric susceptibility assay against Mycobacterium tuberculosis H37Rv (ATCC 27294). In addition, isolated compounds were also evaluated for their effect on lipopolysaccharide-stimulated macrophages for production of pro-inflammatory cytokines, tumour necrosis factor-α, and interleukin-6.

Antibacterial studies were investigated against predominant pathogenic gram-positive and gram-negative bacteria: Staphylococcus aureus, Pseudomonas aeruginosa, Salmonella Typhi, and Escherichia coli. The releasing studies over a 60-hour period showed an initial burst release within the first 8 hours followed by slow release over a prolonged period. Overall results proved that preparations can find potential application in the field of antimicrobial wound dressings and antioxidant activity.

Evidence grade: In vitro and preclinical only.

5.6 Mosquito Larvicidal Activity

Larvicidal activity of 12 fractions and a compound of chloroform extract of Clerodendrum phlomidis L. (Lamiaceae) was assayed for their toxicity against the early fourth-instar larvae of the filarial vector Culex quinquefasciatus and the dengue vector Aedes aegypti. The compound pectolinaringenin was tested at 5, 2.5, 1.0, and 0.5 ppm concentrations. Among the different fractions, fraction 5 recorded the lowest LC₅₀ and LC₉₀ values against both species. The compound pectolinaringenin showed LC₅₀ values of 0.62 ppm and 0.79 ppm against C. quinquefasciatus and A. aegypti, respectively.

5.7 Psychopharmacological / CNS Effects (Sedative, Anti-amnestic)

The alcoholic and aqueous extracts were reported active as analgesic, antidiarrhoeal, antiplasmodial, hypoglycaemic, minor tranquilisers, anti-asthmatic, antifungal, nematicidal, anti-amnestic, and anti-arthritic in the comprehensive 2010 review of the published literature. The CNS-depressant properties were characterised using animal behavioural models including the Y-maze and rotarod test.

The leaves of Clerodendrum phlomidis are traditionally recognised for their rich phytochemical composition and are believed to possess antidiabetic, antidepressant, and anti-Alzheimer's potential.

5.8 Hepatoprotective Effects

Antihepatotoxic activity of the chloroform, petroleum ether, and methanol fractions of Clerodendrum phlomidis whole plant has been assessed by biochemical parameters and histopathological studies against toxicity caused by carbon tetrachloride. The plant is also reported to have diuretic, antidiabetic, antidiarrhoeal, antimicrobial, antioxidant, antiasthmatic, and hepatoprotective activity.

Evidence grade for CNS/hepatoprotective/anti-amnestic: In vitro and preclinical animal data; no controlled human studies found in the indexed literature.

6. Body Systems and Health Areas of Association

Pharmacological studies have shown that compounds and extracts from the Clerodendrum genus have extensive activities, such as anti-inflammatory and anti-nociceptive, anti-oxidant, anti-hypertensive, anticancer, antimicrobial, anti-diarrheal, hepatoprotective, hypoglycaemic, and hypolipidaemic, as well as memory-enhancing and neuroprotective activities. For C. phlomidis specifically, the body systems supported by published preclinical evidence include:

• Musculoskeletal system: Anti-inflammatory and antiarthritic effects, with multiple independent animal studies.
• Respiratory system: Traditional antiasthmatic use, in vitro smooth muscle relaxation data, and a recent preclinical pulmonary fibrosis study.
• Endocrine / Metabolic system: Hypoglycaemic, hypolipidaemic, and anti-obesity effects in rodent models.
• Nervous system: Sedative and anti-amnestic effects reported in rodent behavioural studies.
• Gastrointestinal system: Anti-diarrhoeal effects documented in animal models.
• Hepatic system: Antihepatotoxic data from CCl₄ models.
• Antimicrobial / Infectious disease: In vitro antibacterial and antitubercular data.
• Vector control: Larvicidal activity against mosquito vectors documented in vitro.

7. Dosage Forms and Doses Reported in Studies

The following dose ranges appear in the cited preclinical literature. These are animal or preparation-specific doses reported in studies; no validated human dosage has been established by a regulatory authority or systematically reviewed clinical trial.

• For anti-arthritic activity, the active crude ethanol extract was administered at concentrations of 100, 200, and 400 mg/kg body weight.
• For anti-inflammatory activity, the aqueous extract of root bark (CP) was used at a dose of 21.6 ml/kg.
• In an antiarthritic study, petroleum ether, ethyl acetate, and alcoholic leaf extract was administered orally at doses of 100, 200, and 400 mg/kg body weight from day 13 to day 21.
• A 28-day chronic antidiabetic study used ethanolic leaf extract test groups receiving 100, 200, and 400 mg/kg, with the standard group receiving glibenclamide 2.5 mg/kg.
• The methanolic root extract at 200 and 400 mg/kg was used in the high-fat diet obesity model.
• Methanolic extract of leaves at doses of 200, 400, and 600 mg/kg was used in the psychopharmacological study, with significant reductions in spontaneous activity and exploratory behaviour at these doses.
• The isolated compound HMSB was studied at doses of 25, 50, and 100 mg/kg (intragastrically) for anti-inflammatory and anti-arthritic effects.
• The dose yielding maximum hypoglycaemic effect was reported as 120 mg/kg b.w./p.o.
• In a subchronic toxicity study, aqueous extract of leaves was given orally at doses of 200, 400, and 800 mg/kg/day for 90 days.

In traditional Ayurvedic practice, formulations such as Dashamoola kwath (decoction) are prepared by taking approximately 1 tola (approximately 10–12 g) of coarsely powdered multi-herb material as one dose and boiling it with approximately 16 times water (about 160–200 ml). However, the contribution of C. phlomidis specifically within such multi-herb formulations cannot be determined from these preparations alone.

8. Safety Considerations

Acute and Subchronic Toxicity Data

In a preclinical anti-obesity study, the LD₅₀ value for the methanolic root extract was found to be more than 2000 mg/kg.

A dedicated subchronic toxicity study administered the aqueous extract of Clerodendrum phlomidis leaves orally at doses of 200, 400, and 800 mg/kg/day for 90 days. General behaviour, mortality, animal body weight, food and water consumption were observed throughout the study period, and haematological, biochemical parameters and histopathological analysis were done at the end. No mortality and abnormal behaviour was observed in rats exposed to all three dose levels.

No mortality or abnormal behaviour was observed in rats receiving an aqueous extract of C. phlomidis leaves orally at doses of 200, 400, and 800 mg/kg/day for 90 days, as noted in an independent review of the Clerodendrum genus.

Subacute toxicity studies (500–2000 mg/kg) confirmed that the ethanolic leaf extracts of C. phlomidis L. are non-toxic and harmless at 100, 200, and 500 mg/kg.

CNS-Depressant Potential

Because the methanolic leaf extract has been shown in animal models to potentiate phenobarbitone-induced sleeping time and cause significant reductions in spontaneous activity and muscle relaxant responses at doses of 200–600 mg/kg, MECP caused significant reduction in spontaneous activity and decreases in exploratory behavioural profiles, and significantly potentiated phenobarbitone sodium-induced sleeping time in the doses examined. This indicates a CNS-depressant interaction with barbiturate-class sedatives in animal studies; the clinical relevance for humans has not been established.

Lack of Human Safety Data

Irrespective of its widespread traditional use, no data on subchronic toxicity in humans had been described as of the relevant publication. No regulatory body (EMA, FDA, EFSA, WHO) has issued a formal monograph, safety opinion, or approved health claim for Clerodendrum phlomidis as a stand-alone supplement as of available records. The available safety evidence is limited to preclinical rodent studies.

Botanical Identity Confusion

Agnimantha includes two main types: Laghu Agnimantha (Premna integrifolia) and Brihat Agnimantha (Clerodendrum phlomidis), and these two distinct species are sometimes conflated in traditional texts and commercial products. Misidentification of the source material is therefore a documented concern for botanical preparations labelled as "Agnimantha."

Standardisation and Quality

To ensure identity and quality of the plant material, a TLC method was developed to quantify the marker constituents L-DOPA, lupeol, and β-sitosterol from the leaves, yielding values of 0.06806, 0.01733, and 0.06324 % w/w, respectively. This TLC procedure may be used effectively for identity and quality evaluation as well as quantitative determination for this plant or its derived products.

9. Current Evidence Summary and Research Gaps

Wide clinical uses in traditional medicine have inspired researchers to investigate the pharmacological properties of Clerodendrum and to validate the uses of different species as therapeutic remedies. More and more studies have shown that extracts or active compounds isolated from Clerodendrum species exhibit a wide range of pharmacological activities.

Nevertheless, the 2010 comprehensive review explicitly noted that there are coincidences between some of the traditional usages of this plant and experimentally observed effects of the extracts, but very few biological studies are available on bioactive fractions and/or pure compounds. This characterisation remains broadly accurate: while dozens of preclinical studies have been published since then, no peer-reviewed randomised controlled trials in human subjects have been identified in the indexed biomedical literature for any of the indications described above. Researchers studying C. phlomidis in a pulmonary context stated in 2024 that clinical trials are necessary.

Although above 400 species of the genus Clerodendrum are distributed all over the world, only a few of them have been investigated and studied so far. Terpenes represent the major characteristic constituents with significant biological activities and have great potential to be developed into new drugs. In addition, important activities such as anti-hypertensive, anti-obesity, and hepatoprotective activities indicate that the Clerodendrum genus can be a promising source of biologically active compounds for these diseases.

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