Helicteres isora L. (East Indian Screw Tree)
1. Identity and Botanical Profile
Scientific Classification and Nomenclature
Helicteres isora L. is a deciduous shrub or small tree belonging to the family Malvaceae, usually growing to a height of 3–6 meters, though some specimens can extend up to 8 meters. It is widely known as the "East Indian screw tree," a name derived from its characteristic spirally twisted fruit. In Ayurveda, the plant is known as Avartani. It is commonly known as Marodphali and Marorphali in Hindi, Enthani in other vernacular languages, due to the screw-like appearance of its fruit. In Sanskrit, the plant is also referred to as Avartaphala. In Bangladesh, it goes by the names Atmora or Rajot.
Taxonomy Note
The plant has also been classified within the family Sterculiaceae, which is now treated as a subfamily of the more broadly defined Malvaceae under modern APG classification. This dual family attribution appears in the scientific literature, with older studies citing Sterculiaceae and more recent sources using Malvaceae.
Natural Distribution and Morphology
The species is native to tropical Asia and is distributed across India, Sri Lanka, Nepal, Myanmar, and Thailand. Tropical and subtropical regions with high to intense rainfall are ideal for the plant's growth. It thrives on sandy, lateritic, and loamy soils, and in its natural environment — which often includes wastelands, high slopes, forest border areas, and dry hardwood woodlands — it grows well as a wild shrub and occasionally in semi-cultivated settings. Within India, it occurs often gregariously throughout the country, from the Yamuna eastwards to Bihar and Bengal and southwards in central, western, and southern India and the Andaman Islands.
Morphologically, the species is identified by its characteristic twisted, screw-like follicles and pubescent leaves, and it is adapted to dry deciduous habitats. Its ovate, hairy leaves with serrated margins are arranged alternately, and its bark is grey. Its fruits are green when raw, brown or grey when dried, and twisted, with a screw at the tip. Its flowers are brick red or orange-red.
Plant Parts Used and Common Dosage Forms
The roots, stem, bark, and fruits of H. isora are used for medicinal purposes. The leaves, seeds, fruits, and roots of this plant have been used in Ayurvedic treatment. Common preparations reported in the traditional and research literature include:
- Aqueous decoctions and hot water extracts of the fruit and bark
- Ethanolic and hydroalcoholic extracts of the root
- Powdered dried fruit (administered with milk in traditional pediatric practice)
- Juice of raw roots
In traditional pediatric Ayurvedic practice, Marod Phali is used in children above two years of age for diarrhea and abdominal colic pain in very small quantities of 250 mg or one pinch along with milk.
2. Traditional and Historical Use
Ayurveda, Siddha, and Unani
In both structured (Ayurveda, Unani, and Siddha) and unorganized (folk, native, and ethnic) forms, people have long used H. isora for medicinal purposes. In Ayurveda, the plant is classified as a "stambhana" (astringent) drug due to its tannin-rich profile. The plant is used in Indian indigenous medicine for the treatment of abdominal colic, cough, and other common disorders.
Traditionally it is being used in the Indian System of Medicine (ISM) to cure various ailments including diarrhoea, dysentery, abdominal pains, diabetes, ulcers, intestinal parasites, and hemorrhages. Fruits of Helicteres isora Linn., commonly called Murudsheng in India, are usually prescribed in the Indian traditional systems of medicine, especially in Ayurveda, for a variety of intestinal complaints.
Folk Medicine Across South and Southeast Asia
Folk medicine in India, Sri Lanka, Nepal, Myanmar, and Thailand similarly employs the plant's bark, root, and fruits for dysentery, intestinal colic, helminthiasis, cough, and as a postpartum restorative. Avartani is used as a folk medicine to treat snakebite, diarrhoea, and constipation of newborn babies. The root juice is also claimed to be useful in diabetes, empyema, and is a traditional cure for snakebite.
The capsule (fruit) has long been employed in intestinal complaints, colic, flatulence, and diarrhea in India. The juice of roots is used in diabetes, emphysema, stomach affections, scabies, and snakebite.
Traditional Rationale
The word Avartani means "rotating." The fruits of Helicteres isora are twisted, which gave the Ayurvedic practitioner an imagination about intestines, and hence they were considered useful in treating intestinal parasites and twitching pain in the abdomen — reflecting the Ayurvedic doctrine of signatures (Yatra Akrutihi Tatra Gunaaha Vasanti).
The root and bark are described in traditional sources as expectorant, demulcent, astringent to the bowels, and a cure for scabies when applied topically.
The plant has been used in the indigenous system of medicine in India for the treatment of diabetes mellitus since time immemorial.
3. Phytochemistry: Key Constituents and Active Compounds
The fruit, leaf, bark, root, and seed of H. isora mainly contain carbohydrates, saponin, tannin, proteins, steroids, anthraquinone glycosides, cardiac glycosides, phenolic compounds, terpenoids, alkaloid salts, free alkaloids, flavonoid glucuronides, α-tocopherol, reduced glutathione, and sapogenin.
Fruits
Identified active ingredients from the fruits include phenols, flavonoids, alkaloids, glycosides, phytosterols, carotenoids, tannins, neolignans, rosmarinic acid derivatives, betulinic acid, daucosterol, anthraquinones, sterols, lupeol, β-sitosterol, α- and β-amyrin, taraxerone, 4′-O-β-D-glucopyranosyl rosmarinic acid, 4,4′-O-di-β-D-glucopyranosyl rosmarinic acid, and a compound named 4′-O-β-D-glucopyranosyl isorinic acid, together with rosmarinic acid, and lignans including (±)-pinoresinol, (–)-boehmenan and (–)-boehmenan H.
Leaves
Flavones such as methyl ether and 7,4′-di-O-methyleisoscutellarein (5,8-dihydroxy-7,4′-flavones), along with kaempferol-3-O-galactoside and herbacetin-8-O-glucuronide, have been isolated from the leaves of H. isora. Additional flavonoid glycosides trifolin and hibifolin have also been identified from the leaves.
Roots
From the roots, work by Saraswatiibhai led to the identification of chloroplast pigments, phytosterols, hydroxyl carboxylic acid, saponins, phlobatannins, sugar, and lignins. A preliminary study by Nair and Grampurohit showed the presence of phytosterols, fixed oils and fats, phenolic compounds, tannins, amino acids, and carbohydrates in seeds. Cucurbitacin B and isocucurbitacin B have been isolated from the root.
Comprehensive Chemical Summary
A comprehensive review of the literature documents the following classes of compounds across the plant's various parts: phytosterols, saponins, sugars, phlobatannins, lignin, triterpenoids and their acetates, cucurbitacin B, isocucurbitacin B, flavonoids, flavonoid glucuronides, neolignans, rosmarinic acid derivatives, tannins, cardiac glycosides, sterols, triterpenes, α- and β-amyrin, lupeol, friedelin, taraxerone, β-sitosterol, and volatile oil.
4. Established Mechanisms of Action
Antidiabetic / Insulin-Sensitizing Mechanisms
Saponins isolated from H. isora show antidiabetic effects by activating the PI3K/Akt pathway, leading to phosphorylation and inactivation of GSK-3α/β with subsequent stimulation of glycogen synthesis as well as increase of GLUT4-dependent glucose transport across the cell membrane.
Western blotting confirmed that incubation with saponins (100 µg/ml) and sapogenin (100 µg/ml) induced the phosphorylation of phosphatidylinositol-3-kinase (PI3K) as well as of the downstream targets protein kinase B/Akt (at Ser473) and glycogen synthase kinase GSK-3α/β (at Ser21/9) in a time-dependent manner. No phosphorylation of the AMP-sensitive kinase AMPK (at Thr172) was observed. Within 48 hours, saponins/sapogenin treatment further increased the protein abundance of the insulin-sensitive glucose transporter GLUT4.
Treatment with saponins caused a significant reduction in the serum lipid and glucose levels and increased the expression of adipsin, PPARγ, and GLUT4, while reducing expression of FABP4 and G6Pase. Saponins are thus beneficial for improving hyperlipidemia and hyperglycemia by increasing the gene expression of adipsin, GLUT4, and PPARγ and reducing the gene expression of the enzyme G6Pase and FABP4 in C57BL/KsJ-db/db mice.
Antioxidant Mechanisms
The hot water extract of Helicteres isora can effectively scavenge various reactive oxygen species and free radicals under in vitro conditions, possibly due to the stable oxidized products it can form after oxidation or radical scavenging. The broad range of activity of the hot water extract suggests that multiple mechanisms are responsible for the antioxidant and antidiabetic activity.
In streptozotocin-diabetic rats, treatment with aqueous bark extract led to an appreciable decrease in peroxidation products (TBARS, conjugated dienes, and hydroperoxides) in heart tissues. The decreased activities of key antioxidant enzymes — superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST), and glutathione (GSH) — were brought back to near-normal range upon treatment.
Antispasmodic Mechanisms
The antispasmodic activity of the fruits was investigated in vitro on guinea-pig ileum against three spasmogens — acetylcholine, histamine, and barium chloride — with IC₅₀ values determined. Activity was compared with standard antispasmodic agents atropine and diphenhydramine hydrochloride, and also studied in vivo by observing gastrointestinal motility in mice.
Antibiotic Resistance Modulation
Shriram et al. reported organic extracts of H. isora as a new and safe plasmid-curing agent, resulting in the possibility of a new type of combination therapy between antibiotics and potential drugs effective against plasmid-encoded multiple antibiotic resistance. The concentrations of the curing agents used were sub-inhibitory, since bacteria were already resistant to these concentrations.
5. Scientific Evidence by Area of Use
5.1 Metabolic / Antidiabetic and Hypolipidemic Effects
Animal studies (preclinical):
Root juice of H. isora has been used in the treatment of diabetes by several ethnic groups in India. A program was initiated by Chakrabarti et al. (2002) to elucidate the scientific basis for this. Ethanolic extract of H. isora root caused significant reduction in plasma glucose, triglyceride, and insulin levels at a dose of 300 mg/kg after 9 days of administration to insulin-resistant and diabetic C57BL/KsJ-db/db mice. In normoglycemic and mildly hypertriglyceridemic Swiss albino mice, the extract also showed significant reduction in plasma triglyceride and insulin levels, without affecting plasma glucose level.
Antihyperglycemic and hypolipidemic activities of H. isora root extracts were investigated in alloxan-induced diabetic rats. Alloxan-induced diabetic rats experienced 69.13 and 51.14% reduction in blood glucose, 22.60 and 21.89% reduction in total cholesterol, 30.12 and 19.96% reduction in triglycerides, and 50.05 and 34.29% reduction in urea levels following oral administration of butanol and aqueous ethanol extracts at 250 mg/kg for 10 days, respectively. The beneficial effects were supported by histological examinations of the liver, pancreas, and kidney.
A study by Bhavsar et al. (2009) characterised saponins as the active antidiabetic constituents of H. isora and evaluated changes in the gene expression of glucose and lipid metabolism-regulating genes in C57BL/KsJ-db/db mice. The mice were divided into four groups: one diabetic control, and three groups treated with methanol extract (100 mg/kg), saponins (100 mg/kg), and pioglitazone (30 mg/kg) for 14 days.
The effect of hot water extract of fruits on glucose uptake was studied in rodent skeletal muscle cells (L-6 cells). Hot water extracts were found to be significantly active at 200 µg/ml, comparable with insulin and metformin. Elevation of glucose uptake in association with glucose transport supported the upregulation of glucose uptake. Hot water extract of H. isora was concluded to activate glucose uptake in L-6 cell lines of mouse skeletal muscles.
The hot water extract of Helicteres isora fruits showed maximum antioxidant activity with an IC₅₀ value of 25.12±0.18 µg/ml for the DPPH assay, an IC₅₀ value of 740.64±4.76 µg/ml for the microsomal lipid peroxidation assay, and 45.63% antioxidant activity in the β-carotene–linoleate model. The extract produced a significant (P<0.05) uptake of glucose by isolated rat hemidiaphragm, though it was less effective than the reference drug metformin. The authors concluded the hot water extract exhibited significant antioxidant activity and moderate antidiabetic activity meriting further investigation.
In streptozotocin-induced diabetic rats, serum and liver lipid levels were abnormal compared to control rats; total cholesterol, triglycerides, phospholipids, LDL, and VLDL were elevated, and HDL level was significantly decreased. After treatment with Helicteres isora fruit extract (HiFE), the lipid levels of diabetic rats were restored to near-normal levels, demonstrating antihyperlipidemic potential.
Human / clinical evidence:
One study reported that an H. isora mixture was effectively used to control glucose levels in the blood in type-2 diabetic patients practicing regular yoga and exercise (Subramanium et al., 2014). However, this study involved a combination of lifestyle interventions, limiting conclusions about the plant extract alone. No controlled, randomised clinical trials of H. isora in human subjects have been identified in the peer-reviewed literature. The totality of evidence for antidiabetic and hypolipidemic effects remains at the preclinical (animal model and in vitro) level.
Evidence strength: Preliminary; animal and in vitro only, with one uncontrolled report in humans. No phase I, II, or III clinical trials have been published.
5.2 Antioxidant Activity
Acetone fruit extract of H. isora showed 96.44% strong antioxidant activity compared to hexane and isopropyl alcohol extracts in dot-plot assays. The aqueous extract of H. isora bark at 100 mg and 200 mg/kg body weight was screened for its antioxidant effect in streptozotocin-induced diabetic rats. An appreciable decrease in lipid peroxidation products and restoration of key antioxidant enzymes (SOD, CAT, GPx, GST, GSH) was observed in the heart tissues of treated diabetic rats. All antioxidant data currently exist from in vitro and animal models only; no human clinical trials evaluating antioxidant endpoints have been published.
Evidence strength: Preliminary; in vitro and animal models only.
5.3 Gastrointestinal — Antispasmodic and Anti-diarrheal Effects
A study by Pohocha and Grampurohit (2001) revealed that fruits are used in the cases of colic pain and diarrhea, a finding that underlines the plant's antispasmodic potential. This was assessed in isolated guinea-pig ileum (in vitro) and by gastrointestinal motility studies in mice (in vivo). No human clinical trials of the antispasmodic or anti-diarrheal effects of H. isora have been identified.
Evidence strength: Preliminary; limited to in vitro and animal models, consistent with traditional use but lacking clinical validation.
5.4 Antimicrobial and Antiplasmid Activity
Water extract of the fruits has been reported to exhibit anti-HIV activity (Otake et al., 1995) and to possess antispasmodic activity. Shriram et al. reported organic extracts of H. isora as a new and safe plasmid-curing agent, raising the possibility of a new type of combination between antibiotics and potential drugs effective against plasmid-encoded multiple antibiotic resistance. These findings are preliminary in vitro results and have not been translated into clinical studies.
Evidence strength: In vitro only; preliminary findings without clinical corroboration.
5.5 Anticancer Activity
Cucurbitacin B and isocucurbitacin B, isolated from the roots, have been identified as cytotoxic components of Helicteres isora. Acetone extract exhibited cytotoxicity against human lung cancer cells (NCI-H460), whereas acetone and crude protein extracts showed activity against reactive oxygen species. Varghese et al. reported that the drug has a potent action against human breast cancer, and that cytotoxic activity is attributed to the presence of alkaloids and flavonoids. All anticancer data are from cell-line (in vitro) studies. No human clinical data exist.
Evidence strength: In vitro only; cytotoxic compounds identified, no in vivo or clinical studies.
5.6 Hepatoprotective Activity
Ethanolic extract of aerial parts of H. isora, possibly due to the presence of phenolics or β-sitosterol, has been observed to show hepatoprotective activity. It has been studied in mice affected by paracetamol-induced liver injury and toxicity (Giang et al., 2021).
Evidence strength: Preliminary; limited to animal models, no human data.
5.7 Antinociceptive (Analgesic) Activity
Aqueous ethanol, petroleum ether, and chloroform extracts showed significant antinociceptive activity. Phytochemical analysis of the active extracts indicated that their major constituents are sterols and triterpenoids (in the petroleum ether extract) and their glycosides (in the chloroform and aqueous ethanol extracts).
Evidence strength: Animal model data only; no clinical studies.
5.8 Hematoprotective Activity
Helicteres isora L. has significant antioxidant properties responsible for its medicinal properties. One study reported that H. isora caused significant improvement in anemia-induced alterations in blood RBCs, Hb, and HCT levels in rats, and restored anemia-induced changes in the liver, kidneys, heart, lungs, spleen, and bone marrow, providing significant protection against phenylhydrazine-induced hemolytic anemia in Wistar rats.
Evidence strength: Preclinical (rat model) only; no human data.
6. Body Systems and Health Areas
The plant shows antidiabetic, antioxidant, anticancer, antinociceptive, antimicrobial, antispasmodic, and anti-inflammatory activities. Based on the totality of the literature, the following body systems and health areas are associated with H. isora:
- Digestive / Gastrointestinal System: Traditional systems employ its fruits, roots, stem bark, and leaves to manage gastrointestinal disturbances, including diarrhea, dysentery, intestinal colic, and helminthiasis.
- Metabolic / Endocrine System: The roots and fruits have been widely used in the traditional system of medicine and reported to possess hypolipidemic and antidiabetic activities.
- Immune / Antimicrobial System: Antibacterial, antiplasmid, and preliminary anti-HIV activities have been documented in vitro.
- Nervous System (Pain): Antinociceptive activity demonstrated in animal models.
- Liver / Hepatic System: Hepatoprotective actions have been pharmacologically investigated.
- Respiratory System: Respiratory ailments and cough are listed among traditional indications across classical and folk systems.
- Cardiovascular / Hematological System: Cardiac antioxidant and antiperoxidative potential, as well as protection against hemolytic anemia, have been studied in animal models.
- Oncology: Cytotoxic constituents identified in vitro; no clinical data.
7. Dosage Forms and Dosages Reported in Studies
The following dosages are reported strictly as they appear in the cited sources and relate to preclinical (animal) models, not clinical recommendations for human use:
- Ethanolic extract of H. isora root: 300 mg/kg body weight administered for 9 days to insulin-resistant and diabetic db/db mice.
- Butanol and aqueous ethanol extracts of H. isora root: 250 mg/kg, orally, for 10 days in alloxan-induced diabetic rats.
- Methanol extract and purified saponins: 100 mg/kg; pioglitazone (comparator): 30 mg/kg, administered for 14 days in db/db mice.
- Hot water fruit extract: significantly active at 200 µg/ml in the L-6 cell line glucose uptake model.
- Aqueous extract of bark: 100 mg and 200 mg/kg body weight in streptozotocin-induced diabetic rats.
- In a pre-clinical safety study, oral administrations of graded doses of 500, 1000, and 1500 mg/kg body weight were administered to experimental rats for 14 days. In a second phase, higher doses of 3,000, 4,000, and 5,000 mg/kg body weight were administered to assess acute toxicity.
- Traditional Ayurvedic pediatric dose of Marod Phali: 250 mg or one pinch with milk in children above two years of age for diarrhea and abdominal colic.
No standardized human clinical dosage has been established through controlled trials. No regulatory agency (WHO, EMA, FDA, CDSCO) has published an approved or recommended dose for H. isora preparations.
8. Safety Considerations
Pre-clinical Toxicology
The ethanolic root extract of H. isora has been shown to have low acute toxicity (LD₅₀ > 5 g/kg) and low cytotoxicity in C2C12 cells (IC₅₀ > 0.4 mg/mL) in preclinical assessment. Acute toxicity studies in mice using the Weil method were conducted alongside the antispasmodic activity study (Pohocha and Grampurohit, 2001).
Contradictory Evidence Regarding Diabetes-Related Safety
One study observed that consumption of H. isora affects fat accumulation, adipocyte differentiation, and adiponectin transcription, which the authors suggested may not be suitable for the prevention of diabetes (Siripurkpong and Fungkrajai, 2020). This finding stands in contrast to other preclinical work demonstrating antidiabetic benefits and highlights unresolved mechanistic questions regarding the plant's effects on adipogenesis via PPARγ modulation.
Gaps in Safety Data
Despite the wealth of research supporting pharmacological claims, the translation of H. isora into clinical therapeutics has been limited by inconsistencies in extraction methods, phytochemical standardization, and the lack of comprehensive safety profiles. No human safety or tolerability studies, drug-interaction studies, or chronic toxicity data in humans have been published in peer-reviewed journals.
The roots and seeds contain cucurbitacin B and isocucurbitacin B, which are documented cytotoxic principles — a consideration of relevance when root preparations are used, particularly at higher doses or over extended periods.
Limitations of the Evidence Base
In vitro and in vivo studies have demonstrated that H. isora exhibits antidiabetic, antihyperlipidemic, hepatoprotective, anti-inflammatory, antioxidant, and antidiarrheal activities. These pharmacological properties align with its traditional uses and present promising potential for developing novel therapeutic agents. Despite this, the translation into clinical therapeutics has been limited by inconsistencies in extraction methods, phytochemical standardization, and the lack of comprehensive safety profiles.
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