1. INTRODUCTION:

In many cultures and traditions around the world, the ethnobotanical significance of medicinal plants primarily helped to sustain public health for a certain time¹ It is essential to note that, according to the World Health Organisation (WHO), plants are the primary source of nutrition for approximately 80% of the world's population. Additionally, as phytotherapeutic compounds, around 11% of important medications are derived from plants² Only a small amount of research has been conducted to support the use of traditional medicines in Nepalese communities, even though the majority of them utilise them to treat illnesses. To establish a connection between traditional use and scientific understanding, it is essential to investigate the chemical components and biological activities of plants and plant products that impact human biochemistry in medicinal plants. With more than 120 species, Heracleum is one of the largest genera in the Umbelliferae family. In Asia, there are 109 species in the Heracleum genus. Hogweed and cow parsnip are two common names of their respective genera³ They are commonly known as Budho aushadhee, Bhote jeeraa, Bhutakesh, phaakee in Nepal; Trunag, Tunakin Bhutanese; Chimping in Sikkimese.

Traditional uses for Heracleum species, often known as hogweed, include seasonings, food additives, and flavouring. In addition, these plants are frequently used in folk medicine to treat a variety of ailments, including inflammation, flatulence, stomachaches, epilepsy, psoriasis, and as carminative, wound-healing, antibacterial, anti-diarrheal, tonic, digestive, painkilling, analgesic, and anticonvulsant agents. The pharmacological properties of the Heracleum genus are diverse, including anti-inflammatory, antibacterial, anticholinesterase, antioxidant, antiviral, cytotoxic, and anticarcinogenic properties. The Heracleum genus of plants has yielded 94 identified compounds, all of which suggest essential biological functions.

Additionally, about 50 substances have been recognized as significant constituents in their essential oils. The genus possesses a wealth of different bioactive coumarin compounds, and there is considerable potential for discovering new coumarins. Heracleum species produce essential oils with a wide range of biological activity, primarily aliphatic esters and monoterpenes. Due to their extensive ethnobotanical uses and pharmacological properties, Heracleum species offer considerable promise for use in the food, cosmetics, fragrance, and pharmaceutical industries⁴. Some Heracleum species are employed as antipyretics, analgesics, and diaphoretics in conventional medicine. Tetrataenium nepalense D. Don. (Umbelliferae) grows along the sides of streams in Sikkim, Himalaya. The plant's root is said to possess a variety of therapeutic properties, including antibacterial, anti-diarrheal, tonic, and aphrodisiac effects⁵.

Figure 1: Tetrataenium nepalense

Figure 2: Dry form of Tetrataenium nepalense

Picture credit: Saroj Kasaju; efloraofindia

2. BOTANY AND TAXONOMY:

Robust, with a build-up to two meters high, featuring a cylindrical root about 15cm long. It has a pubescent, solitary stem. The basal leaves are long-petiolate, with broad-ovate leaf blades measuring 20–45 × 20–35cm, trifoliolate or 1-pinnate, with 3–7 pairs of pinnae; the leaflets are broadly ovate, 9–20 × 5–12cm, slightly pubescent on both sides—more notably along the veins—and have serrated margins. Similar to the basal leaves, the cauline leaves are smaller, three-lobed, sessile, and droop downwards on enlarged sheaths. The rays are numerous, ranging from (8–) 15–60 (or more), each 6–9cm long; they are unequal and extend during fruiting. The bracteoles are 5–8 in number, linear, unequal, measuring 5–9mm, and persistent. The umbellule consists of 8–30 flowers, and the umbel spans 11–30cm wide; bracts are 1–5 in number, linear or absent. The teeth of the calyx are subulate. The outer flowers of the umbel are notably bright, with white, sometimes pinkish, petals that are two-lobed and up to 3 × 2.3mm in size. Young ovaries are covered with many hairs. The fruit is oblong, measuring 9-11 (up to 17) × 7–10 (up to 14)mm; vittae are filiform and solitary in the dorsal furrows, extending to two-thirds the length of the mericarp, with 1–2 in the lateral furrows, shorter than the dorsal, and 2–4 on the commissure, roughly two-thirds as long as the mericarp. The dorsal ribs are filiform, and the lateral ribs are extensively winged, with wings 2.2–4 mm wide on the plane of the seed face. The flowering period occurs in February and September. The Sino-Himalayan region is home to thirty-two species of this genus, of which twenty-five are found in southwest China, nine in the Indian Himalayan region, and eight in Nepal⁶.

Table 1: Scientific classification of T. nepalense

Kingdom	Plantae
Phylum	Streptophyta
Class	Equisetopsida
Sub class	Magnoliidae
Order	Apiales
Family	Apiaceae
Genus	Heracleum
Synonmy	Heracleum nepalense

Figure 3: Geographical area highlighting the availability of T. nepalense in India.

3. ETHNO-MEDICAL USE:

Throughout Nepal, between 1,800 and 3,700 metres, roasted foods made from the seeds of Heracleum nepalense are consumed⁷ Heracleum nepalense, belonging to the family Apiaceae, is commonly used for the common cold and cough by the local healers called ‘Dhami-Jhanki⁸.The inhabitants of the Sikkim Himalayan region have successfully treated a variety of inflammatory ailments using the root of this plant, despite a lack of scientific research on the subject⁹. In addition to being used as a household spice, it is also utilised for its medicinal properties, including digestive, carminative, and antidiarrheal effects. Tetrataenium nepalense root is also said to have antioxidant and antibacterial properties¹⁰. For the treatment of influenza and sinusitis, the dried fruits of Heracleum wallichii DC. are chewed by local people¹¹. It is also used as a breath rate stimulator, a blood pressure stimulator, an antidiarrheal, a tonic, and an aphrodisiac¹². In the steep parts of Sikkim and the Himalayas, its fruits are frequently utilised as a spice, flavouring, and ethnomedicine. The fruits are mostly used in Sikkim to treat stomachaches and intestinal gastritis, while they are also occasionally used as a food ingredient, appetiser, and digestive aid.¹³

4. MATERIALS AND METHODS:

Search engines PubMed, Scopus, Web of Science, and Google Scholar, from the database's inception in August 2025, were used in combination with the terms "Heracleum nepalense" or "Tetrataenium nepalense". Reference lists of included studies and genus-level reviews were hand-searched.

5. PHYTO-CONSTITUENT:

Numerous plant species from the genus Heracleum have undergone phytochemical and pharmacological analysis, and numerous compounds have been extracted and characterised. Furanocoumarins, including bergapten, byakangelicol, phellopterin, xanthotoxin, isopimpinellin, and imperatorin, are abundant in the genus Heracleum¹⁴. T nepalense sample powder was dissolved in four different solvents based on their polarity (n-hexane> diethyl ether > acetone > methanol). Through biochemical testing, the phytochemical makeup of all the extracts was analysed. The phytochemical analysis of the extract identified the presence of terpenoids and alkaloids in the diethyl ether extract of T. nepalense. Hexane and acetone extracts had equal efficacy, with LC₅₀ (Lethal Concentration) values of 116.78ppm and 112.74ppm, respectively. Terpenoids were found in both extracts through biochemical testing of these two extracts. In addition, steroid content in the acetone extract was found. With an LC₅₀ value of 167.57ppm, the methanol extract demonstrated the least amount of mortality³. The presence of essential phytoconstituents such as flavonoids, alkaloids, glycosides, saponins, terpenoids, reducing sugars, polyphenols and quinones was confirmed by the phytochemical screening of the T nepalense from methanol extract^15.

T. nepalense were subjected to phytochemical assays to examine the phytocomponents, including phenol, flavonoid, tannin, saponin, steroid, alkaloid, carbohydrate, protein, and fat. It was extracted with two solvents, methanol and acetone. Solvent extraction with methanol yielded positive results for phytoconstituents, including tannins, phenols, saponins, alkaloids, proteins, and amino acids. For the acetone extract of H. nepalense, the only phytoconstituents present were flavonoids, fixed oil, and fat¹⁶. Upon fractionation with petroleum ether, acetone, and ethyl acetate, the concentrated methanol extract made from the T. nepalense root was obtained. Preliminary phytochemical group testing revealed the presence of reducing sugar, proteins, tannins, flavonoids, steroids, and flavones. A compound (flavonoidal glycoside) was also isolated^17. The root extract of H. nepalense was tested using phytochemical analysis, where successive extractions with petroleum ether, ethyl acetate, and acetone were performed. After being purified, the ethyl acetate portion of the crude extract produced the primary fraction A (flavonoid), along with a few fatty components^18. The roots were macerated in double-distilled water: 99% pure alcohol (30:70 %, v/v) after being filtered, condensed, and eventually lyophilized. The extract underwent column chromatographic separation on silica gel (60–120 mesh) using a hexane: ethyl acetate mixture as the eluent. By using IR, 1H and 13C-NMR, MS, and X-ray crystallographic investigations, the isolate's (100% purity) identity was determined. The T. Nepalense root hydroalcoholic extract yielded the furocoumarin bergapten as an isolate. Bergapten's ability to photosensitize is widely documented (Levine et al., 1989). Additionally, it has impressive antibacterial, anticancer, and anti-inflammatory properties.^18.

Table 2: Active Compounds and Proposed Mechanisms of Heracelum Species

Compound	Compound class	Evidence of occurrence in Heracleum	Reported bioactivity in literature	Reference
Bergapten	Furanocoumarin	Reported from Heracleum species and specifically linked to H. nepalense root work	Anti‑inflammatory effects; inhibits NLRP3 inflammasome and promotes mitophagy in cellular models	⁽¹⁹⁾⁽²⁰⁾
Imperatorin	Furanocoumarin	Detected in roots of several Heracleum taxa (quantified in comparative phytochemical work	Anti‑inflammatory activity reported in genus studies	⁽²¹⁾
Xanthotoxin (8‑methoxypsoralen)	Furanocoumarin	Detected in Heracleum spp.; furanocoumarins commonly detected in roots/fruit/essential extracts of Heracleum and are reported or expected in H. nepalense chemotypes.	Phototoxicity; anti-inflammatory; antimicrobial; anticancer (reported for some furanocoumarins).	⁽²¹⁾⁽³⁾
Umbelliferone, scopoletin, osthol, limettin)	coumarins	Detected across Heracleum genus; reported in Heracleum extracts and genus reviews	Anti-inflammatory, antioxidant, enzyme-modulating (e.g., cholinesterase in some Heracleum spp.).	⁽³⁾
Caryophyllene oxide Cadinene, cadinol	Sesquiterpenes cadina derivatives Cadina derivatives	Identified by GC-MS in H. nepalense extracts.	Antimicrobial, insecticidal, anti-inflammatory (reported for some sesquiterpenes).	⁽²²⁾
"Phenylpropanoids	aromatic ethers / allylbenzenes)	Myristicin and related compounds reported in Heracleum essential oils.	Psychoactive/toxic at high dose (myristicin); insecticidal/antimicrobial at extract concentrations.	⁽²²⁾
Essential-oil terpenoids and aromatic volatiles	limonene, β-pinene myristicin octyl acetate/hexanoate/octanoate	Reported major volatiles in several Heracleum species and in essential-oil analyses (also GC-MS of H. nepalense extracts found terpenoids).	Antimicrobial, insecticidal/larvicidal, anti-inflammatory (some terpenes).	⁽²²⁾
Phenolics / general antioxidants (total phenolics)	Phenolic compounds	Reported antioxidant activity in H. nepalense root/fruit extracts (DPPH/FRAP in published bioassays).	Antioxidant, anti-inflammatory (indirect), cytoprotective.	⁽²¹⁾
Crude extract activities (whole-plant studies)		H. nepalense root and fruit extracts tested for: antioxidant, antimicrobial, larvicidal (Aedes), immune stimulation (older studies) and some anti-inflammatory bioassays.	Antioxidant; antimicrobial; larvicidal (notably against Aedes albopictus); immune stimulation (increased macrophage phagocytosis reported historically).	⁽¹⁵⁾
Hexadecanoic acid methyl ester (methyl palmitate), 9,12-octadecadienoic acid methyl ester (linoleic methyl ester), oleic/other FAMEs	Fatty acid methyl esters (FAMEs).	Abundant in GC-MS of H. nepalense fruit and methanolic extracts (reported compositional study).	Larvicidal (mosquito), antioxidant (some FAs), weak antimicrobial (reported in extract bioassays).	⁽¹⁵⁾

5. PHARMACOLOGICAL ACTIVITY:

5.1. Anti-microbial activity:

The agar well diffusion method was used to conduct the antimicrobial assay. T. nepalense test plant extracts were diluted in 0.25 per cent dimethyl sulfoxide (DMSO) to create a stock concentration of 100mg/ml, and it was sterilised by filtration through a 0.45μm cellulose acetate membrane filter (Sartorius). The stock concentration was used to create various concentrations of methanol and acetone extracts (10mg/mL, 25mg/mL, 50mg/mL, 75 mg/mL, and 100mg/mL). A negative control was employed, consisting of DMSO (0.25%). A positive control was utilised, consisting of gentamicin (0.1 mg/ml). Using the agar well diffusion method, the potency of the plant extracts was tested against the following bacterial strains: Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Proteus vulgaris, Staphylococcus aureus, Bacillus cereus, and Bacillus subtilis. The extract inhibited the growth of Escherichia coli and most Gram-positive bacteria. T. nepalense inhibited Bacillus subtilis at its maximum zone of inhibition (13.75±0.5mm). Klebsiella pneumoniae, Pseudomonas aeruginosa, and Proteus vulgaris did not exhibit any growth inhibition in response to the plant extracts in methanol. The MIC value was between 15 and 100mg/mL⁸. An antimicrobial test was performed in vitro and in vivo using the methanolic extract of T. nepalense. (in vitro model). Significant in vitro antimicrobial activity was demonstrated by the methanol extract of the T. nepalense root against 257(Gram-positive and Gram-negative bacteria, including multi-resistant Staphylococcus (MRS) strains. All three of the reference MRSC bacterial strains were discovered to be sensitive to the extract at a dosage of 1000µg/ml. Out of 257 bacteria, the root extract inhibited the growth of 197 isolates at a concentration of 128 to 512µg/ml, 57 isolates at a dose of l000 mg/ml, and the final three isolates at a concentration of >2000 µg/ml, according to the results of the antimicrobial spectrum test. Antimicrobial activity was also evaluated for the isolated compound II (flavonoidal glycoside). The outcome showed that all isolates were sensitive to compound II at concentrations ranging from 128 to 256µg/mL. It was interesting to see that compound II, at a dosage of 128µg/ml, was sensitive to all of the MRSC strains (in vivo model) The protective ability of T. nepalense methanol extract and compound II against S. typhimurium NCTC 74 results showed that no mice died in a control group receiving only the extract, but 3 out of 20 mice died in the bacterial challenge and actual test dose of the extract at 128 mg/g body weight. In the test groups, 8 mice perished after receiving the bacterial challenge and extract at a dose of 50mg/ml body weight, followed by 5 mice at a dose of 256mg/ml, 12 mice at a dose of 512 mg/ml, and so on. Fifteen of the 20 mice in the control group, which received only the bacterial challenge, perished. Further research with compound II showed that no mice died in a control group that received only compound II. In contrast, only two out of twenty mice perished in the bacterial challenge, and the actual test dose was 100mg/ml body weight for mice, as reported by Pramila, Koirala et al. (17). The efficacy of a methanol extract from the roots of T. nepalense against Gram-positive and Gram-negative bacteria that cause diarrhoea was investigated in this study. The minimum inhibitory concentration (MIC) was also determined. Shigella dysenteriae, Escherichia coli, Shigella boydii, Vibrio cholerae, and Salmonella typhimurium, were among the examined bacterial strains, and it was shown that the root extract's antibacterial activity decreased in the order listed above. The extract also demonstrated bactericidal properties. The presence of some antibiotic component in the root may be the cause of its antibacterial ability against bacteria that cause diarrhoea⁵.

5.2. Anti-Inflammatory:

An investigation aimed to assess the effect of bergapten on the cytokine generation by human peripheral blood mononuclear cells (PBMCs) during inflammation (Bergapten is widely known for its ability to cause photosensitization, Levine et al., 1989). By using Ficoll-Hypaque centrifugation, PBMCs were separated. TNF (Tumor Necrosis Factor) has been reported to drive the synthesis and secretion of numerous cytokines and also engage in the inflammatory process by activating T-cells, macrophages, and fibroblasts. The bergapten demonstrated concentration-dependent suppression of TNF- and IL-6 production by PBMCs. As a result, stopping the synthesis of TNF stops the inflammatory process¹⁴.

5.3. Anti-oxidant Activity:

The extracts of T. nepalense showed a dose-dependent inhibitory effect on the DPPH free radical scavenging activity. The DPPH (2,2-diphenyl-1-picrylhydrazyl) scavenging activity increased significantly (p 0.05) with an increase in the concentration of the plant extracts. The amount of the extract (measured in g/ml) that removes 50% of DPPH radicals is known as the IC₅₀ value. Ascorbic acid had an IC₅₀ (Half-Maximal Inhibitory Concentration) value of 20g/ml and a percentage inhibition of 54.37 0.27%. T. nepalense had a concentration of 60g/ml and an inhibition percentage of 53.29 0.27%. Flavonoid was not found in the methanol extract of T. nepalense fruits, which may be related to the plant's comparatively poor antioxidant activity. The observed antioxidant effects of the test plant extracts could be attributed to the presence of phenolic compounds combined with other phytochemicals (15). The impact of compound II and a methanol extract of T. nepalense root on the lipid peroxidation caused by ferrous sulphate in goat liver homogenate. The outcomes showed that the highest prevention of lipid peroxidation (69.25±1.21%) was achieved at a concentration of 1000 µg/mL of the methanol extract. On the other hand, the standard medication vitamin E revealed an inhibition percentage of 73.42±2.3 at a 5mM concentration. The DPPH scavenging capacity of the methanol extract was determined to be 72.38±3.92% at a 1000µg/ml concentration in the study on the effect of methanol extract and compound II on DPPH radical scavenging. The compound II, on the other hand, displayed 76.38 5.12% at a concentration of 50µg/ml. The IC₅₀ value of the extract was found to be 6.0mg/mL. The root extract effectively prevented the degradation of deoxyribose caused by hydroxyl radical at a concentration of 1000 µg/m, as compared to that of the well-known scavenger mannitol (89.64±4.62%), according to the effect of root extract and compound II on scavenging of hydroxyl radical¹⁸.

5.4. Immunostimulation Activity:

Methanol extract of T. nepalense root and its isolated compound (flavonoidal glycoside) were used for the immunostimulation activity test. To create appropriate dosage forms, the root extract, as well as isolated components, were suspended individually in a 1% solution of sodium carboxymethylcellulose. Either male or female Swiss Albino mice, weighing 17–25g each, were used. For immunisation and challenge, sheep red blood cells (SRBCs) were adjusted to a concentration of 1 × 10^8 cells in 0.1mL after being rinsed three times with normal saline. Eight groups of mice were created, each with ten mice. For seven days, Group I (Control) received 1% sodium carboxy methyl cellulose in water (0.3 ml/mouse), Groups II through V received methanol extract in varying concentrations (250–1,000mg/kg, p.o.), Group VI received the standard medication, levamisoie (50mg/kg, p.o. ), and Groups VII and VIII received compound I (25 and 50mg/kg, p.o.) for seven After seven days, mice from each group received an injection of carbon ink suspension (10!ll/gm body weight) into the tail vein. The results demonstrated a considerable increase in carbon clearance from the blood using the methanol extract at doses of 250–1,000mg/kg and its isolated component at doses of 25–50mg/kg. The highest carbon clearance for the methanol extract at 1000 mg/kg was 0.158±0.01 (P < 0.05), and for the isolated drug at 50 mg/kg, it was 0.160±0.018 (P < 0.05), while the clearance value for levamisole was 0.164±0.016⁷. Additionally, they demonstrated that the mice's carbon clearance, delayed-type hypersensitivity, and antibody titer all increased significantly. T nepalense exhibited a dose-dependent immunostimulant effect, which could be attributed to the flavonoid content or due to the combination with other component (s)²⁴.

5.5. Anti-Diabetic Activity:

The in vitro alpha-amylase inhibition activity of Heracleum nepalense methanol extracts was investigated in relation to their alpha-glucosidase inhibitory impact. Heracleum nepalense, which is native to Nepal, appears to have modest alpha-amylase inhibitory action, according to the study's preliminary findings²³.

5.7 Toxicological profile and safety:

The diethyl ether extract of T. nepalense was analysed using GC-MS. Sesquiterpene and furanocoumarin concentrations were determined to be high. To protect themselves against herbivores, plants from the Apiaceae and Rutaceae families naturally produce furanocoumarins, which are harmful secondary metabolites²⁵. The most prevalent and potent substances in plant essential oils were sesquiterpenes. According to this study, Heracleum nepalense contains a variety of secondary metabolite classes that are harmful to mosquito larvae¹⁵. The T. nepalense fruits were subjected to an Inductively Coupled Plasma (ICP) examination, which identified a variety of components that were divided into various groups according to their parts per billion (ppb) concentration. Given their traditional usage, the study's goal was to examine the elements content of T. nepalense fruits to emphasise their medicinal relevance. However, it was observed that several elements, such as lead and arsenic, were present. There is little documentation of the toxicological study, and no thorough research on this topic of safety and toxicology has been done¹³.

6. CONCLUSION:

Tetrataenium nepalense, also referred to as Heracleum nepalense, is found in regions such as Sikkim, Darjeeling, and Nepal. Most commonly with its geographical availability, this Himalayan plant has a very long history of traditional uses for digestion, inflammation, infection and immune-related conditions. With more than 120 species, Heracleum is one of the largest genera in the Umbelliferae family. With more than 120 species, Heracleum is one of the largest genera in the Umbelliferae family. While only focusing on one particular species, that is Tetrataenium nepalense, researchers have found the plant to be rich in biologically active compounds, especially furanocoumarins, flavonoids, terpenoids, and other classes of phytochemicals, which are responsible for its potent ethnomedicinal uses like anti-microbial, anti-inflammatory, anti-oxidant, immunomodulator, and potential anti-diabetic properties. Although herbal or ethnomedicinal plants have their own pros and cons, if not consumed or taken carefully, as research has suggested, the shining bright side of T. nepalense for several diseases, but also some parts of research highlight the risk of safety concerns as well presence of toxic furanocoumarins and trace of heavy metals like lead and arsenic has been noted, no comprehensive toxicological evaluation has been performed till date. This highlights the need for further safety studies, especially for potential pharmaceutical use. While there is substantial evidence to prove the therapeutic potential of T. nepalense, additional studies are needed to fully characterize its toxicological profile, understand its mechanism of action and efficacy in clinical settings. T. nepalense has a promising future as a new source of functional food and phytopharmaceutical, but needs very careful consideration of both efficacy and safety.

7. DECLARATION OF INTEREST:

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

8. ACKNOWLEDGEMENTS:

We would like to sincerely express our gratitude to the institutions, North Bengal University and Himalayan Pharmacy Institute, for giving us a research platform.

9. ABBREVIATIONS:

WHO- World Health Organisation; T nepalense- Tetrataenium nepalense; H nepalense - Heracleum nepalense; LC₅₀ -Lethal Concentration; FAMEs- Fatty acid methyl esters; DMSO- dimethyl sulfoxide; MIC- minimum inhibitory concentration; PMBCs- peripheral blood mononuclear cells; TNF - Tumor Necrosis Factor; DPPH- 2,2-diphenyl-1-picrylhydrazyl; IC₅₀ - Half-Maximal Inhibitory Concentration; SRBCs- sheep red blood cells; GC-MS- Gas Chromatography- Mass Spectrometry; ICP- Inductively Coupled Plasma; PPB- parts per billion.

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Received on 14.01.2026 Revised on 17.02.2026

Accepted on 21.03.2026 Published on 21.04.2026

Available online from April 24, 2026

Res. J. Pharmacognosy and Phytochem. 2026; 18(2):149-155.

DOI: 10.52711/0975-4385.2026.00021

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

Phytochemical and Pharmacological Insights into Tetrataenium nepalense: An Integrative Review