Therapeutic Potential of Aconitum heterophyllum:

A Review on Phyto-pharmacological properties

 

Anna Mathew¹, Chandrashekar. K. S¹*, Anoop Kishore², Vasudev Pai¹, Aswatha Ram H. N¹, Ramadevi Pemmereddy¹

¹Department of Pharmacognosy, Manipal College of Pharmaceutical Sciences,

Manipal Academy of Higher Education, Manipal - 576104, Karnataka, India.

²Department of Pharmacology, Manipal College of Pharmaceutical Sciences,

Manipal Academy of Higher Education, Manipal - 576104, Karnataka, India.

 

ABSTRACT:

Aconitum heterophyllum, a medicinal herb commonly used in Ayurveda, which belongs to the Ranunculaceae family and is known to have a number of therapeutic properties. Root tubers of this plant are commonly used in pediatric medicine for fever management. It has also been used as an antipyretic, antibacterial, anthelmintic, antitussive, anti-inflammatory, and antidiarrheal agent. The root tubers are rich sources of diterpene alkaloids, which may be one of the reasons for the medicinal properties. Required data on this plant were obtained from electronic sources (Google scholar, PubMed, Scopus, Web of Science), several classical textbooks on Ayurveda, and ethnopharmacology. This review article covers all the relevant information on its pharmacological and phytochemical aspects. In this study, we have critically reviewed recent advancements of Aconitum heterophyllum in order to validate its usage as a multipurpose therapeutic agent.

 

 

 

INTRODUCTION: 

Aconitum heterophyllum, also known as Indian atees or ativisha, is an important medicinal herb in Ayurveda and has been used as the main ingredient in many Indian ayurvedic formulations, as well as Bhutanese and Chinese herbal medicines¹. The plant species, usually found on the high altitude alpine and subalpine meadows in the Western Himalayas, usually 3000 to 4200 m altitude, some of which descend to 2200 m. In general, sandy textured soils with rich organic matter, for cultivation, and sandy loam and acidic soil, for seed germination have been recommended².

 

Since the plant belongs to the genus Aconitum, which is highly toxic in nature, this medicinal herb has been reported to be the least toxic among the species³. The root tubers of Aconitum heterophyllum are said to have a bitter taste and a cooling potency.

 

They have been used as expectorant, febrifuge, anthelmintic, antidiarrhoeal, antiemetic, and anti-inflammatory agents⁴. It is a major ingredient of Balchaturbhadra churna, which is used for fever, diarrhea, bronchitis, upper respiratory tract infections, asthma, vomiting, and several other pediatric problems^5,6.

 

Historical Background:

The name Aconitum comes from the Greek word akónitos, which derives from the Greek word akóne, meaning whetstone. The genus Aconitum contains around 350 species of flowering plants in temperate regions of the Northern Hemisphere, most of which are found in China. The genus comprises mainly two subgenera, Lycoctonum and Aconitum⁷. In 1727, Carl Linnaeus noticed splendid stands of Aconitum lycoctonum growing in Lapland. Later, in his pioneering work on botanical nomenclature, he defined the name of the genus and the description of a variety of species. Throughout the preliterary ancient world of Europe, aconites were regarded mainly as arrow or bait poisons and used with extreme caution. Common names illustrate this usage: wolfsbane or lycotonum, leopardsbane or pardalianche, beast killer, or theriophionon⁸.

 

In Southern Europe, myth and folk culture developed, possibly based on an earlier oral history, which connected aconites with illegal poisonings and enigmatic, perhaps villainous motives. Ancient Greeks and Romans, for example, found aconites to be dangerous herbs, correlated with both intentional and unintentional poisoning, and since they were toxic, ineligible for use in herbal pharmacies⁹. In ancient ayurvedic literature, aconite is often prescribed for topical use in ointments and salves, particularly for pain relief. During the nineteenth century, aconite became a popular commodity in regular pharmacies in Europe and the United States¹⁰. The homeopathic medicine practice in Europe and the United States also treats aconite, in dilute preparations, as an essential medicine with multiple applications^11,12.

 

Table 1. Taxonomical classification¹³

Kingdom	Plantae
Division	Magnoliophyta
Class	Magnoliopsida
Order	Ranunculales
Family	Ranunculaceae
Genus	Aconitum
Species	Aconitum heterophyllum

 

Botanical Description:

Indian Atees is a perennial herb, 1-4 feet tall, characterized by its rather large greenish-purple, prominently darker-veined, and its coarsely toothed but otherwise entire leaves¹⁴. Roots of the plant are tuberous, conical, thicker at its upper extremity, tapering towards lower extremity, and they may be white or grey in color. The stem can be branched or simple and is usually 15 to 90 cm tall. The stem emerges from a biennial tuberous root that produces a new tuber every year, the old tuber dying after the plant flowers¹⁵. Leaves are heteromorphous and glabrous. The flowers are hooded, which may be white or violet in color, and usually occur as inflorescence. Seeds may be pyramidal, shortly hairy, brownish, or blackish in color^16,17.

 

Figure 1.  Aconitum heterophyllum herb and roots

 

Table 2. General description of Ativisha

Different aspects	Description	Ref.
Habitat	High altitude alpine and sub-alpine meadows in the Western Himalayas	18
Parts used	Root tubers	1
Flowers	Large, hooded, white to violet in color and appear in slender racemes or lax leafy panicles. Corolla is hairy, and the carpels are five in number with 10-18 follicles	2
Flowering and fruiting	August-October
Leaves	Usually 5-lobed, glabrous, and heteromorphous with long petioles and blades are ovate-cordate or orbicular-cordate in outline	19
Stem	Erect, simple or branched, 15-20 cm in height, Crispo-pubescent in the upper and glabrous in the lower part
Roots	Conical, fusiform, or cylindrical (2 to 8 cm long and 0.4 to 1.5 cm broad) smooth or slightly longitudinally wrinkled, marked with a few whitish scars of rootlets, yellowish to greyish white externally and starchy and chalky white internally	20
Chemical constituents	Alkaloids, carbohydrates, saponins, glycosides, flavonoids, terpenoids	21
Traditional uses	Bronchitis, Cough, upper respiratory tract infections, common cold, malaria, vomiting,  diarrhea, indigestion	22
Preclinical Studies	Anti-diarrheal activity, Anti-hyperlipidemic and anti-obesity activity, Anti-inflammatory activity, Antibacterial and antifungal activity, Antioxidant and Nephroprotective activity, Anticholinesterase activity, Antidiabetic activity, Immunomodulation activity, Antiulcer activity, and Anthelmintic activity	23-29 30-33

 

Table 3. Vernacular names³⁴

English	Indian atees
Sanskrit	Aruna, Ativisa
Hindi	Atis
Malayalam	Ativitayam
Kannada	Athivisha
Tamil	Adhividayam
Telugu	Ativasa

 

Genetics:

In order to recognize possible genes involved with the development of root tubers of Aconitum heterophyllum, a study was conducted to analyze the transcriptomes of root tubers by taking hints from genes involved in other plant species. qPCR revealed that out of 18 genes, eight genes encoding ADP-glucose pyrophosphorylase (AGPase), GDP-mannose pyrophosphorylase (GMPase), SRF receptor kinase, RING-box protein 1(RBX1), Expansin, β-amylase, and Auxin responsive factor 2 (ARF2), SHAGGY displayed higher expression of transcripts in roots (13-171 folds) compared to shoots³⁵. Another study provided a report on quantitative expression analysis of 15 genes of mevalonate and non-mevalonate pathways on roots versus shoots of Aconitum heterophyllum and identified their possible role in aconite biosynthesis³⁶. Relatively higher expression of 4 genes of the MVA pathway (HMGR, HMGS, IPPI, PMK) and four genes of the MEP pathway (ISPD, DXPS, GDPS, HDS) in roots compared to shoots showed a positive correlation with atisine content³⁷.

 

Phytochemical Profile:

Aconitum species are chemically characterized by an abundance of alkaloids and flavonoids, most of which have a wide range of pharmacological effects³⁸. The biologically active constituents present in this medicinal plant are alkaloids, flavonoids, flavanol glycosides, diterpenoids, and non-diterpenoid compounds¹⁹. The rhizomes of the plant have been known for many years to contain atisine as the major constituent, which makes them classified as the simpler aconitum alkaloids with low toxicity³⁹. The presence of chemical constituents such as Atisine, Atidine, Hetisine, Atisenol, F-dihydroatisine, Heteratisine, Heterophyllidine, Heterophylline, Heterophyllisine, Hetidine, Hetisinone, β-sitosterol, carotene, and isoatisine are assumed to be responsible for the major pharmacological properties of the medicinal plant⁴⁰.

 

A comprehensive analysis of the basic constituents of the Aconitum heterophyllum root was conducted, and major diterpene alkaloids were isolated. The strong base fraction comprises the bulk of alkaloids, mainly Atisine, Atidine, and Isoatisine. The weak base fraction of which lactonic fraction consists of heteratisine, heterophyllisine, heterophylline, and heterophyllidine. The alkaloids of very strong base fraction yielded hetisine, hetidine, hetisinone³⁹. Another study was performed in which heterophyllinine-A and heterophyllinine-B, the new two diterpene alkaloids, as well as two known alkaloids, lycoctonine, and dihydroatisine were isolated from the roots of Aconitum heterophyllum wall²⁹. Inorder to study the antibacterial activity of norditerpenoid alkaloids, two novel aconitine-type norditerpenoid alkaloids, such as 6-dehydroacetylsepaconitine and 13-hydroxylappaconitine, along with three known nor diterpenoid alkaloids lycoctonine, delphatine and lappaconitine, were isolated from the roots of Aconitum heterophyllum wall⁴¹. In an in vitro anticholinesterase and antioxidant  potential analysis of diterpene alkaloids, three new diterpene alkaloids such as 6β-Methoxy,9β-dihydroxy heteratisine, 1α,11,13β-trihydroxylhetisine, and 6,15 β-dihydroxylhetisine were isolated by means of NMR and mass spectroscopy as well as single X-ray crystallography⁴².

 

Figure 2. Major Chemical Constituents of Aconitum heterophyllum

 

Structure of major chemical constituents

 

Classical Uses:

Aconitum heterophyllum is a multipurpose solution to various ailments in Ayurveda. It has been used as anthelmintic, antipyretic, anti-inflammatory, astringent, analgesic, and febrifuge⁴³. It is beneficial for the traditional treatment of coughs, diarrhea, and indigestion. It is a valuable drug for infants with diarrhea, fever, and vomiting. Traditionally, it has been used as an antidote to poisoning⁴⁴. Inflammatory bowel syndrome, Haemorrhoids are also relieved with the use of Atis preparations. It is helpful for general detoxification of the body, for detoxifying blood and body tissue⁵. This herb is considered as the best home remedy for treating malaria⁴⁵. The root powder of Ativisha with honey is recommended for upper respiratory problems such as cough and bronchitis. It acts as an anthelmintic, effective against guinea worms. The aqueous pulp is effective in regulating blood pressure as it has a hypotensive effect. It is also useful in treating Diabetes Mellitus (Type II). It functions as a strong aphrodisiac and is also useful as a diuretic¹¹. The herb is beneficial for infants and children as a safe medicine for gastroenteric fevers. This natural herb is designated as one of the principle drug for neuralgia by Homeopathy⁴⁶. It is also beneficial for rheumatism and acts as a nerve sedative⁴⁵. For tonsillitis, seeds that have crumbled in honey are applied topically on the throat. Root vapors inhalation is helpful for headaches, particularly in migraine¹⁹.

 

In Ayurveda, the root forms an ingredient in a variety of ayurvedic formulations; Amritarishta (immunity booster), Chandraprabha Vati (urinary tract infection, male sexual dysfunction, benign prostatic hyperplasia, Mennorahgia, diabetes-induced fatigue), Yograj Guggulu (arthritis), Mahasudarsan churna, Balchaturbhadra churna and Astivisachurna (fever, diarrhea, and vomiting)⁴⁷. In Unani, the roots are utilized as an astringent in bleeding piles, Amenorrhea, and Leucorrhoea and are an ingredient of Majun Bawasir, Sufuf Babis, Majun Jograj Guggulu, and Majun Murrawahul-Arwah⁴⁸. The fine powder is used as a bitter tonic in diarrhea and malabsorption syndrome. The root tubers are useful in a number of illnesses such as gastrointestinal and bilious complaints, intermittent fevers, diarrhea, dysentery, bacterial infections, and are used as aphrodisiac and anti-inflammatory agent⁴⁹.

 

Pharmacological Profile:

Evaluation of Aconitum heterophyllum (A. heterophyllum) for its therapeutic potential by scientific studies has proved that it possesses anti-diarrhoeal, anti-inflammatory, anti-hypertensive, anti-bacterial, anti-obesity, hypolipidemic, anticholinergic properties. Besides, it also exhibits antioxidant activity and immunomodulatory effects.

 

Table 4. Pharmacological Profile of Aconitum heterophyllum

Preclinical Studies	Extract	Model	Dose	References
Anti-diarrheal	Ethanolic	Fecal excretion and castor oil-induced diarrhea	50, 100, 200 mg/kg p.o	23
Anti-hyperlipidemic and anti-obesity	Methanolic	High fat diet induced obese rat	200, 400 mg/kg p.o	24, 25
Anti-inflammatory	Ethanolic	Cotton pellet-induced granuloma	225, 450, 900 mg/kg p.o	26
Antibacterial and antifungal	Chloroform	Disc diffusion method	12.5, 25, 50, 100 µg/disc	41, 50
Nephroprotective	Ethanolic	Glycerol induced renal failure	250, 500 mg/kg p.o	28
Antioxidant	Ethanolic	DPPH, NO, H2O2, and FRAP assay	25-800 µg
Anticholinesterase	Chloroform	Modified Ellman’s method	0.1 mM	29, 42
Antidiabetic	Methanolic	STZ induced diabetic rat	200 mg/kg	30
Antiulcer	Ethanolic	Pylorus ligation method	200.400 mg/kg	32
Anthelmintic	Ethanolic/Aqueous	Pheritema postuma model	10-100%	33
Immunomodulatory	Bala Compound	Umbilical cord blood Ig status and changes in Ig levels	5 drops	31

 

Anti-diarrheal activity:

The anti-motility and anti-secretory property of the roots of A. heterophyllum has been studied via PGE₂ enteropooling test and castor-oil induced intestinal fluid accumulation study. The root extract showed significant anti-diarrheal activity as a consequence of stimulation of Na⁺ and K⁺ATPase function mediated by the nitric oxide pathway. It also acts by a mechanism of either reduced mucosal secretion or enhanced mucosal absorption, causing the feces to become dry and hence slowing their passage through the colon²³.

 

Anti-hyperlipidemic activity and anti-obesity activity:

The orally administered A. heterophyllum extract in diet-induced obese rats markedly reduced serum total cholesterol, triglycerides, and LDL cholesterol levels and was also found to inhibit intestinal fat absorption.  The change in lipid profile by A.heterophyllum treatment is due to the inhibition of HMGR and the activation of LCAT enzymes. According to this observation, it can be comprehended that the A. heterophyllum fraction exhibits potential hypolipidemic and anti-obesity activity^24,25.

 

Anti-inflammatory activity:

In order to assess the anti-inflammatory activity of A. heterophyllum, a cotton-pellet induced granuloma rat model was used. The extract was observed to lower the weight of cotton pellet granuloma in a dose-dependent manner, and the higher dose of A.heterophyllum reduced inflammation in a way that was very similar to diclofenac sodium’s inhibitory effect. The anti-inflammatory activity of the extract is assumed to be due to the interruption of Arachidonic acid metabolism and inhibiting prostaglandin synthesis at the late phase of inflammation²⁶.

 

Antibacterial activity and antifungal activity:

Isolation of the roots of A. hetrophyllum wall yielded two novel aconitine-type norditerpenoid alkaloids, 13-hydroxylappaconitine and 6-dehydroacetylsepaconitine, as well as three known norditerpenoid alkaloids lycoctonine, delphatine and lappaconitine, all of which showed considerable antibacterial activity⁴¹. Sinam and his team conducted a study that established the antibacterial property of alkaloid extracts of A. heterophyllum root against different bacteria, including human pathogens, and it was assumed that the antibacterial activity of root alkaloid extract was due to the synergistic effect of alkaloids²⁷. The in-vitro antifungal activity of A. heterophyllum extract was determined by measuring diameters of inhibitory zones of the extract against Aspergillus niger and Alternalia solani. It showed significant antifungal activity against both the tested strains⁵⁰.

 

Antioxidant and Nephroprotective activity:

The antioxidant activity of A. heterophyllum was assessed in vitro using the Nitric oxide radical scavenging assay, DPPH assay, hydrogen peroxide, and ferric reducing antioxidant power assays and was found to be equal to the antioxidant activity of Vitamin C. The nephroprotective activity of ethanolic extract of A. heterophyllum root was investigated in glycerol-induced acute renal failure in Wistar albino rats, and the extract showed a significant nephroprotective effect by attenuation of renal function test parameters and histopathological changes of the kidney compared to the glycerol treated group²⁸.

 

Anticholinesterase activity:

Five known compounds, hetisinone, iso-atisine, 19-epi-isoatisine, heteratisine, and atidine and three novel diterpenoid alkaloids, 1α,11,13β-trihydroxylhetisine, 6β-Methoxy,9β-dihydroxylheteratisine, and, 6,15 β-dihydroxylhetisine and were isolated and characterized from the roots of A. heterophyllum wall. All these compounds were screened for their cholinesterase (AChE and BuChE) enzyme inhibition activities, followed by in-silico studies that indicated the potential role of these alkaloids in the treatment of nervous disorders such as Alzheimer disease⁴². Heterophyllinine-A and heterophyllinine-B (two new diterpenoid alkaloids) were isolated from the roots of A. heterophyllum Wall and found to inhibit AChE and BuChE enzymes in a concentration-dependent manner, and also these compounds found to have thirteen times more specific activity against BuChE than AChE²⁹.

 

Antidiabetic activity:

The study on the antidiabetic activity of A. heterophyllum root extract was focused on assessing the effect of root extract on plasma and tissue glycoprotein components in streptozotocin-induced diabetic rats. In diabetic rats, there was a substantial rise in the plasma glycoprotein levels as well as significant reduction in the Sialic acid level and resulting massive elevation in hexosamine, fucose, and hexose levels in the liver and kidney. A. heterophyllum root extract’s oral administration in streptozotocin-diabetic rats markedly reverted the hexosamine, hexose, fucose, and sialic acid levels towards normal values, and indicating that A. heterophyllum has a normalizing effect on glycoprotein components³⁰.

 

Antiulcer activity:

The antiulcer property of A. heterophyllum extract was evaluated in Wistar albino rats against pylorus ligation-induced ulcers. The extract showed a reduction in free and total acidity, total proteins, and an increase in pH of gastric content and total carbohydrate to protein ratio. The gastroprotective activity of this plant extract is mainly attributed to inhibiting the generation of damaging free radical cascades and oxidant radical release³².

 

Anthelmintic activity:

The alcoholic and aqueous root extract of A. heterophyllum at different concentrations ranging from 10 to 100 % showed dose-dependent anthelmintic activity against Pheritema postuma, most commonly known as Indian earthworm. It was assumed that the flavonoids and alkaloids might be responsible for the anthelmintic activity of the plant³³.

 

Immunomodulation activity:

The immunomodulating activity of A. heterophyllum, along with several other medicinal plants, was examined on delayed-type hypersensitivity, skin allograft rejection, humoral responses to sheep RBCs, and phagocytic activity of the reticuloendothelial system in mice. A. heterophyllum extract was observed to promote phagocytic activity while suppressing the humoral component of the immune system⁵¹. The clinical study of the immunoglobulin-enhancing effect of the Bala compound on infants was studied by Rao and his team (2009). Ativisha (Aconitum heterophyllum), one of the major ingredients of the Bala compound, was given to newborns in oral drops formulation for a period of six months and the result showed a significant increase of immunoglobulins IgG, IgM, and IgA in serum³¹.

 

CONCLUSION:

Aconitum heterophyllum, belongs to the Aconitum genus, which has roughly 250 species around the globe. The majority of the species are found in the north Himalayas region mainly Uttarakhand belts. The plant taxonamy is of typical Ranunculus, the leaves are palmate, the flower is the raceme, and the fruit are the follicle aggregates. The detailed literature survey revealed that Aconitum heterophyllum is an important source of various medicinally and pharmacologically important drugs. The major chemical constituent, diterpene alkaloids which is responsible for a number of pharmacological activities such as anti-inflammatory, antidiabetic, antioxidant, antidiarrheal, etc. while Aconitum heterophyllum has been employed successfully in Ayurvedic medicine for centuries for the treatment of various pediatric ailments like fever, diarrhea, indigestion, inflammation, helminthiasis, and hyperlipidemia, more clinical trials should be performed to support its therapeutic usage. It is also vital to identify that Aconitum heterophyllum extracts may be useful not only isolation but may have a modulating impact when given along with other herbs or drugs combination.

 

ACKNOWLEDGEMENTS:

The authors would like to acknowledge the facilities provided by the Manipal College of Pharmaceutical Sciences and Manipal Academy of Higher Education in executing this review article.

 

REFERENCES:

1.     Ayurwiki. Aconitum heterophyllum - Ativisa, Indian Atees. In 2020. Available from: https://ayurwiki.org/Ayurwiki/Aconitum_heterophyllum_-_Ativisa,_Indian_Atees

2.     Vikaspedia. Aconitum heterophyllum. In 2020. Available from: https://media.vikaspedia.in/agriculture/crop-production/package-of-practices/medicinal-and-aromatic-plants/aconitum-heterophyllum

3.     Nyirimigabo E, Xu Y, Li Y, Wang Y, Agyemang K, Zhang Y. A review on phytochemistry, pharmacology and toxicology studies of Aconitum. Journal of  Pharmacy and Pharmacology. 2015;67(1):1–19. 

4.     Narapusetty N, Sivaiah O, Balanasaraiah B, Haranadhbabu M, Prasad B, Crown BH, et al.  Anti-Inflammatory activity of Ethanolic extract of Basella alba in acute and Sub-acute Model . Asian Journal of Pharmaceutical Research. 2017;7(2):88.

5.     Singh J. Ativisha – Aconitum Heterophyllum. In: Ayur Times. 2017. Available from: https://www.ayurtimes.com/ativisha-aconitum-heterophyllum/

6.     Raju V, Bell JJ, Merlin NJ, Dharan SS.  Ethno Pharmacological Uses of Artocarpus altilis -A Review . Asian Journal of  Pharmaceutical Research. 2017;7(4):239.

7.     Hao D-C. Genomics and Evolution of Medicinal Plants. Ranunculales Medicinal Plants. Elsevier Inc.; 2018. 1–33 p. Available from: http://dx.doi.org/10.1016/B978-0-12-814232-5/00001-0

8.     C. KR, Y. CR. Ethnopharmacology, Phytochemistry and Pharmacology of Adenanthera pavonina L. (Mimosaceae). Research Journal of Pharmacology and Pharmacodynamics. 2019;11(4):140–6.

9.     Rajan D, K J, Hamza A, Rishana F. Comparative Review on Pharmacognostical and Pharmacological activities of Ocimum Species. Research Journal of Pharmacognosy and  Phytochemistry. 2020;12(1):37–46.

10.  A J, Maurya A, Verma SC, Srivastava A, Shankar MB, Sharma RK. A Brief Review on Pharmacognosy, Phytochemistry and Therapeutic Potential of Solanum Indium L. used in Indian Systems of Medicine. Asian Journal of Research in Chemistry. 2016;9(3):127–32.

11.  Been A. Aconitum : Genus of Powerful and Sensational Plants. JSTOR. 1992;34(1):35–9.

12.  Kumawat N, Pantwalawalkar J, Vispute Y, Tade R, Nangare S. An Overview on Phytochemistry, Pharmacology, Pharmaceutical, Traditional and Economical Aspects of Aegle marmelos. Asian Journal of Pharmacy and Technology. 2021;11(2):166–74.

13.  NHP. Atees. In: National Health Portal. 2018. Available from: http://nhp.org.in/en/unani/840-atees

14.  Singh G. Greenish Himalayan Monkshood. In: Flowers of India. 2011. Available from: https://www.flowersofindia.net/catalog/slides/Greenish Himalayan Monkshood.html

15.  Fern K. Aconitum heterophyllum. In: Useful Temperate Plants Database. 2016. Available from: http://temperate.theferns.info/plant/Aconitum+heterophyllum

16.  Chauhan M. Atis, Ativisha (Aconitum heterophyllum) - Properties, Benefits, Uses & Dosage. In: Planet Ayurveda. 2019. Available from: https://www.planetayurveda.com/library/atis-ativisha-aconitum-heterophyllum/

17.  Chaudhari RD, Girase PR, Suryawanshi HP, Pawar SP.  A Review on Tridax procumbens Linn . Asian Journal of Pharmacy and Technology. 2018;8(3):158.

18.  Beigh SY, Nawchoo IA, Iqbal M. Cultivation and conservation of Aconitum heterophyllum: A critically endangered medicinal herb of the Northwest Himalayas. Journal of  Herbs, Spices and Medicinal Plants. 2006;11(4):47–56.

19.  Buddhadev SG, Buddhadev SS. A complete review on Ativisha -Aconitum heterophyllum. Pharma Science Monitor. 2017;8(1):111–4.

20.  ICMR. Aconitum heterophyllum Wall.ex Royle (Ativisa). In: Quality Standards of Indian Medicinal plants. 2006. p. 2.

21.  Paramanick D, Panday R, Shukla SS, Sharma V. Primary pharmacological and other important findings on the medicinal plant “Aconitum Heterophyllum” (Aruna). Journal of Pharmacopuncture. 2017;20(2):89–92.

22.  Jaiswal R, Kaushik J, Sharma R. Ativisha as a drug of choice in pediatric ailments. World Journal of Pharmaceutical and Medical Research. 2020;6(7):132–5.

23.  Prasad SK, Jain D, Patel DK, Sahu AN, Hemalatha S. Antisecretory and antimotility activity of Aconitum heterophyllum and its significance in treatment of diarrhea. Indian Journal of Pharmacology. 2014;46(1):82–7.

24.  Subash AK, Augustine A. Hypolipidemic effect of methanol fraction of Aconitum heterophyllum wall ex Royle and the mechanism of action in diet-induced obese rats. Journal of Advanced Pharmaceutical Technology and Research. 2012;3(4):224–8.

25.  Jain SK, Jain R, Jain N. Antiobesity potential of Aconitum Heterophyllum roots. International Journal of Pharma and Bio Sciences. 2019;10(3):65–74.

26.  Verma S, Ojha S, Raish M. Anti-inflammatory activity of Aconitum heterophyllum on cotton pellet-induced granuloma in rats. Journal of Medical Plants Research. 2010;4(15):1566–9.

27.  Sinam YM, Kumar S, Hajare S, Gautam S, Devi GAS. Antibacterial property of Aconitum heterophyllum root alkaloid. International Journal of Advanced Research. 2014;2(7):839–44.

28.  Gopala V, Konda R, Eerike M, Raghuraman LP, Rajamanickam MK. Antioxidant and Nephroprotective Activities of Aconitum heterophyllum Root in Glycerol Induced Acute Renal Failure in Rats. Journal of Clinical and Diagnostic Research. 2016;10(3):3–7.

29.  Nisar M, Ahmad M, Wadood N, Lodhi MA, Shaheen F, Choudhary MI. New diterpenoid alkaloids from Aconitum heterophyllum Wall: Selective butyrylcholinestrase inhibitors. Journal of Enzyme Inhibition and Medicinal Chemistry. 2009;24(1):47–51.

30.  Ahmad Rah T, S. H, C. E. Influence of Aconitum heterophyllum Wall. ex Royle root extract on Plasma and Tissue glycoprotein components in streptozotocin induced diabetic rats. International  Journal of Advanced Research and Biological Sciences. 2016;3(2):27–34.

31.  Rao A., R.D S, P KG, A.J.V. SP. Clinical study of the Immunoglobululin Enhancing Effect of “ Bala compound ” on Infants. Ancient Sci Life. 2009;28(3):18–22.

32.  Rajakrishnan R, Alfarhan AH, Al-ansari AM, Lekshmi R, Sreelakshmi R, Benil PB, et al. Therapeutic efficacy of the root tubers of Aconitum heterophyllum and its substitute Cyperus rotundus in the amelioration of pylorus ligation induced ulcerogenic and oxidative damage in rats. Saudi Journal of Biological Sciences. 2020;27(4):1124–9.

33.  M. Pattewar A, Pandharkar T.M, Yerawar P.P, Patawar V.A. Evaluation of In-Vitro Antihelminthic Activity ofAconitum Heterophyllum. Journal of Chemical, Biological and Physical Sciences. 2012;2(4):2401–7.

34.  D K Ved, Suma Tagadur Sureshchandra, Vijay Barve, Vijay Srinivas, Sathya Sangeetha, K. Ravikumar, Kartikeyan R., Vaibhav Kulkarni, Ajith S. Kumar, S.N. Venugopal, B. S. Somashekhar, M.V. Sumanth, Noorunissa Begum, Sugandhi Rani, Surekha K.V.  and ND. Plant Details for a Aconitum heterophyllum Wall. Ex Royle. In: ENVIS Centre on Medicinal Plants. 2016.

35.  Malhotra N, Sood H, Chauhan RS. Transcriptome-wide mining suggests conglomerate of genes associated with tuberous root growth and development in Aconitum heterophyllum Wall. Biotechnology. 2016;6(2):1–8.

36.  Kale N, Rathod S, More S, Shinde N. Phyto-Pharmacological Profile of Wrightia tinctoria. Asian Journal of Research in Pharmaceutical Sciences. 2021;11(4):301–8.

37.  Malhotra N, Kumar V, Sood H, Singh TR, Chauhan RS. Multiple genes of mevalonate and non-mevalonate pathways contribute to high aconites content in an endangered medicinal herb, Aconitum heterophyllum Wall. Phytochemistry. 2014;108:26–34.

38.  Gajalakshmi S , Jeyanthi P , Vijayalakshmi S. Phytochemical Constituent of Aconitum S Pecies-a Review. Int J Appl Biol Pharm Technol. 2011;2(4):121–7.

39.  Pelletier SW, Aneja R, Gopinath KW. The alkaloids of Aconitum heterophyllum wall : isolation and characterization. Phytochemistry. 1968;7(1942):54–7.

40.  Anil  joy pulikkottil. ATIVISA - Aconitum heterophyllum. In: Encyclopedia of Ayurvedic Medicinal Plants A Candle of Medicinal Herb’s Identification and Usage. 2012. Available from: http://www.indianmedicinalplants.info/d2/Aconitum-heterophyllum(Ativisa ).html

41.  Ahmad M, Ahmad W, Ahmad M, Zeeshan M, Shaheen F. Norditerpenoid alkaloids from the roots of Aconitum heterophyllum Wall with antibacterial activity. Journal of Enzyme Inhibition and Med Chemistry. 2008;23(6):1018–22.

42.  Ahmad H, Ahmad S, Shah SAA, Latif A, Ali M, Khan FA, et al. Antioxidant and anticholinesterase potential of diterpenoid alkaloids from Aconitum heterophyllum. Bioorganic Med Chem. 2017;25(13):3368–76.

43.  Puri HS. Uses of Aconites. Journal d' Agriculture Tropicale et de Botanique Appliquee. 2018;21:239–46.

44.  Shyaula SL. Phytochemicals, Traditional Uses and Processing of Aconitum Species in Nepal. Nepal Journal of Science and Technology. 2012;12:171–8.

45.  Ukani MD, Mehta NK, Nanavati DD. Aconitum heterophyllum (ativisha) in ayurveda. Ancient Sci Life . 1996;16(2):166–71.

46.  Bharskar GR. Review on Phytochemistry and Pharmacological Aspects of Pedalium murex Linn. Asian Journal of Research in Pharmaceutical Sciences. 2020;10(3):183–8.

47.  Cheriyan BV, scarlet S, Priyadarshini, Joshi S, Santhseelan, Mohamed S. Eupatorium triplinerve (Vahl): An Ethnobotanical Review. Asian Journal of  Pharmaceutical Research. 2019;9(3):200.

48.  Kale MPM. A Review Article on Euphorbia hirta uses and pharmacological activities. Asian Journal of  Research in Pharmaceutical Sciences. 2016;6(3):141–5.

49.  Bioinformatics Center S. Aconitum heterophyllum Wall. ex. Royle. In: Sikkim State Council of Science and Technology.2007.

50.  Munir N, Ijaz W, Altaf I, Naz S. Evaluation of antifungal and antioxidant potential of two medicinal plants: Aconitum heterophyllum and Polygonum bistorta. Asian Pacific Journal of Tropical Biomedicine. 2014;4(September):S639–43.

51.  Atal CK, Sharma ML, Kaul A, Khajuria A. Immunomodulating agents of plant origin. i: preliminary screening. Journal of Ethnopharmacology. 1986;18(2):133–41.

 

 

 

Accepted on 06.06.2022           © RJPT All right reserved

Research J. Pharm. and Tech 2023; 16(1):470-476.