Perfumed Ginger (Hedychium Spicatum Sm): An Essential oil-bearing plant

 

Roopal Mittal^1,2*, Prerna Goel², Ajay Singh Kushwah³, Gurjant Ranga⁴

¹PhD Research Scholar, IK Gujral Punjab Technical University, Jalandhar (Punjab) 144601, India.

²Assistant Professor, Pharmacognosy, GD Goenka University, Sohna, Gurugram, India.

³Department of Pharmacology, Amar Shaheed Baba Ajit Singh Jujhar Singh Memorial College of Pharmacy, Bela (Ropar) (Punjab) 140111, India.

⁴Department of Pharmacology, R.K.S.D. College of Pharmacy, Kaithal (Haryana) 136027, India.

 

ABSTRACT:

Hedychium spicatum Buch. Ham. ex D. Don. belonging to family Zingiberaceae, commonly known as kapoor kachri is, an essential oil-bearing species known for its medicinally useful scented rhizomes. The herb forms an important part of various polyherbal formulations cited in various classical texts of Chinese, Tibetian, Indian and Unani origin. The rhizome contains about 4% of essential containing a variety of terpenoids (monoterpenoids, sesquiterpenoids and diterpenoids) with 1, 8-Cineole, camphene, sabinene, β-pinene, myrcene, α-phellandrene as major constituents. It is traditionally used for the treatment of different kinds of pain, inflammation, respiratory and blood disorders. The present study systematically compiles its botany, distribution, cultivation, traditional uses, phytochemistry, IUCN status, pharmacological activities and granted patents with respect to the herb and formulations containing H. spicatum. It adds up to the existing knowledge of the previous reviews on the species with prioritization on metabolic profiling and need to use advanced biotechnological propagation techniques for better conservation of the herb in its natural habitat hence preventing its adulteration in trade markets.

 

 

 

INTRODUCTION:

The genus Hedychium is one of the most popular among 52 genera of Zingiberaceae family known for its diverse use in food, medicine, cosmetics, fragrance, ornamental and essential oil industry. It consists of approx 80 species having attractive foliage, beautiful flowers and sweet fragrance¹. Most of the Hedychium species are cultivated for their essences however their rhizome and aerial parts forms useful raw material for paper industry². Also, these are widely used in ethnomedicine for the treatment of various diseases like nausea, asthma, flu, diarrhea, snake bites, leishmaniasis along with reported antimicrobial property of its essential oils, making it a safer alternatives to synthetic antibiotics, antifungal and insecticides respectively^3-6. Thus the genus is gaining popularity as “Biocides” since biopesticides obtained from plant essential oils do not acquire induced resistance against various insects, microbes and have limited toxic effects on human, animal and other non-targeted organisms^7,8.

 

Various species ie., acuminatum, aurantiacum, bousigonianum, coronarium, coccineum, cylindricum, ellipticum, flavum, forrestii, gardnerianum, greenii, gracile, larsenii, malayanum, matthewiii, roxburghii, spicatum and stenopetalum are the major essential oil containing taxas of Hedychiym genus. For essential oil extraction from Hedychium species, mostly rhizomes are used as they are rich in volatile oils and readily available throughout the year⁹. The monoterpenes and sesquiterpenes constitutes the main compounds of its oil with 1,8-cineole (monoterpene) present in major percentage has been reported as most ubiquitous component in almost all of its species⁸.

 

Among various aromatic species of Hedychium, H. spicatum Sm. (Zingiberaceae) is one of the commercially used medicinal herb having extraordinary therapeutic properties against diabetes^10,11. The rhizome of the herb is basically traded in different crude drug markets all over the world (Figure-1). It is commonly known as Kapur kachari in Hindi, spiked ginger lily or perfumed ginger in English, takhellei in Manipuri, Cao Guo Yao in Mandarin and afer kocher in Amharic¹². The taxonomical hierarchy and various other vernacular names of H. spicatum have been summarized in Table 1 and 2 respectively.

 

Table 1: The taxonomical hierarchy of H. spicatum.

 

Table 2: Vernacular names of H.spicatum, commonly used in different parts of India.

 

It is a small, hardy rhizomatous species that grows to around 1m, bearing green leaves, large orange and white coloured flowers. It is widely used in various medicinal, food, cosmetic and perfumery industries^13,14. The species forms an important ingredient of various traditional medicinal systems like Traditional Chinese medicine (TCM), traditional Tibetan medicine, Indian Medicinal System (Ayurveda) and Unani medicine^12,15. H. spicatum belongs to a diploid genus Hedychium which has chromosome number in the sequence (x) of 9, 10, 11, 12, 14 and 17^16,17. The H. spicatum species have 17 pair chromosomes with estimated DNA size as 2.94 pg (2C) [2875.32 Mbp (2C)] detected by flow cytometry¹⁸.

 

Distribution and Cultivation:

Hedychium spicatum is a perennial herb, native to China (Guizhou, Sichuan, Tibet, Yunnan) and extended up to Himalayas, Myanmar, Thailand and Ethiopia respectively¹⁹. It grows well in both temperate and subtropical climatic conditions found, within an altitude of 1000–2800 m^20-23. In India, it has wide distribution extending from Himachal Pradesh, Arunachal Pradesh, Manipur, Meghalaya, Mizoram, Nagaland, Orissa, Sikkim Darjeeling, Andhra Pradesh to Kerala (hills of Thiruvananthpuram district)^6,24-38.

 

Being a sub-tropical bedding herb, it requires ample sunlight but can tolerate minimum temperatures up to -2°C with an exception of the species found in Germany at -16°C. H. spicatum grows well in moisture-rich, sandy to sandy clay soil with lower pH and low organic carbon content ³⁹. It supports flowering in June-October and fruit formation in October- November³⁸.

 

 

Figure 1: the figure of Hedychium spicatum rhizome.

 

Botanical description:

The Himalayan plant, Hedychium spicatum closely resembles Hedychium coronarium morphologically. The leaves of the spicatum species are sessile, oblong, lanceolate and glabrous (beneath) ranging from 30cm or more in length having long clasping sheaths of width up to 10cm. It bears white-coloured, closely imbricate ascending flowers with large, oblong green bracts densely arranged in terminal spikes (30cm), thus the name spiked ginger lily. Flowers are hermaphrodite with linear anthers (6-8.5mm) and pale red coloured filaments; lanceolate, lip cuneate, deeply bifid, broad Corolla (5-6.3cm), bilobed; segments (2.5cm); linear; white staminodes (2.5cm) with calyx shorter than bract¹³. The fruits are glabrous, globose, capsule type which on ripening exposes numerous small black colored seeds embedded in its red arilus^40,41. The rhizome is yellowish-brown (outer) and whitish brown (inner surface) in colour ranges from 15-20cm in length and 2.0-2.5cm in diameter having numerous scars, rings and visible rudiments of rootlets on the outer surface⁴². Its rhizomes are thick, fleshy having a strong aromatic odour (camphoraceous) and bitter. The histological studies of the rhizome of H. spicatum report the presence of compressed, nearly empty, reddish-brown cells in the epidermal layer⁴³. The parenchyma was delicate and most of the cells were found loaded with starch grains, however, resin (yellowish-coloured) and essential oils were present comparatively less.

 

Ethnomedicinal uses:

Hedychium spicatum is one of the commonly used herbs in preparation of indigenous medicine all over the world as it belongs to the family of aromatic species characterized by the presence of volatile oils and oleoresins specifically in its rhizomatous parts^35,44,45.

 

The species is a common ingredient in 19.43% of 175 known herbal formulations mentioned in the Tibetan medicinal system ⁴⁴. PADMA-28 is one of the important formulations of the species mentioned in the Tibetan medicine system used for the treatment of various inflammatory diseases, peripheral vascular occlusive disease and possess promising results in atherosclerosis, chronic active hepatitis and intermittent claudication⁴⁶. Also, the paste has been reported use in treating impotency in females⁴⁴.

 

The Ayurveda describes the ‘Shati’ (H. spicatum) as pungent, bitter in taste (‘Rasa’); astringent (‘Kashaya’); having light, purification and good penetrating power (Guna’) with high potency⁴⁷. The Indian contemporary literature reports its disease-curing properties for swelling, pain, toothache, halitosis, wound healing, apoplectic convulsions, rheumatoid arthritis and in the treatment of various digestive, blood-related and respiratory disorders^13,47,48. Its rhizome powder is recommended in the daily dose of 1-3 g in Ayurvedic Pharmacopoeia⁴⁹. It is available in Indian markets as an important ingredient of various Ayurvedic formulations such as Eranda paka, Shribahushalo guda, Dantodbhedagantaka rasa, Katphaladi churna, Pippalyadi taila, Aravindasava, Ushirasava, Chandanasava, Sarivadyasava, Amritaprasha ghrita, Pradarantaka lauha, Agastyaharitaki rasayana, Shatyadi kvatha respectively ⁴⁹. Apart from traditional formulations, the herb is commercially being sold in the National and International markets as syrup and tablets under the brand name vomicure and vominil, respectively¹⁴.

 

In India, its rhizomes were used for ages in different forms of food, medicine, cosmetics and perfumes in various parts of the country. However, both the rhizomes and fruits of the herb reports aromatic, tonic, stimulant, astringent, diaphoretic and nutritive properties⁵⁰. Its fruit is cooked along with lentils as savory dishes^51,52. It is used as an important ingredient as perfumed baits for catching fish in southern India. It has been referenced in 233 formulations mentioned in Indian texts with a recorded usage therapeutic index of 10.3%⁴⁴.

 

The fresh rhizomes of the species are cooked along with the food or for preparing chutney in parts of Uttrakhand and Manipur respectively^20,44. The Root powder and its small pieces are chewed along with milk for treating asthma and various internal injuries in districts of Uttrakhand and Andhra Pradesh^25,44,53. However, in Himachal Pradesh, its leaves are used along with wheat straw for preparing mats for better durability. The herb was known for its carminative, digestive and emmenagogue properties, majorly used in the form of powder or decoction obtained from its rhizome part. The powder of the rhizome was considered antimicrobial and used as a poultice for various acnes and pain. It was used as an insect repellent to preserve clothes and employed as an auxiliary in the dyeing industry, imparting a pleasant smell to fabrics. Its camphoraceous rhizomes were reported for perfuming tobacco and prepare perfumed cloth along with henna, known as Malagiri cloth in local markets. Even incense sticks are prepared from the rhizomes in different parts⁴⁴. Further, it has reported use in cosmetology (vanishing creams) and veterinary medicine^49,54. A colored, fragrant powder known as Abir was used to be prepared from the rhizome at various religious ceremonies^10,55.

 

The decoction or powders of the rhizomes is known for their stomachic, carminative, stimulant and tonic properties. In divided dose, it was mentioned to be used in bronchial asthma, cough, chest heaviness, sleeplessness, loss of appetite and pulmonary eosinophilia. A small cup of decoction was recommended twice a day for expectorant, stimulant, stomachic, tonic and vasodilatory effect⁴⁴. For liver and other inflammatory complaints, the rhizome powder (1 tsp thrice a day) is advised traditionally⁵⁶. It is used in dyspepsia, diarrhea, piles, liver complaints, ulcers, skin diseases, rheumatoid arthritis and for promoting hair growth. At several places, people used the roots as an antidote against snakebite. The decoction of the rhizome is being used along with deodar sawdust for the treatment of tuberculosis⁵⁷.

 

Substituents, Adulterants and IUCN Status:

H. spicatum is a highly traded rhizomatic herb for the treatment of liver diseases⁵⁶. Its crude extract forms an important ingredient of syrup and tablets available in both National and International markets in the name of vomicure and vominil.

 

In India, the crude drug is traded in various markets like Delhi, Ramnagar, Sharanpur and Tanakpur for 1015 Rs/Kg, 812 Rs/Kg, 1618 Rs/Kg and 818 Rs/Kg respectively²³.

 

However due to its high demand, overexploitation and low availability as it is a slow-growing plant that matures over 2 to 3 years, it is recorded as vulnerable under threat status by the World Conservation Union (International Union for Conservation of Nature and Natural resources; IUCN)⁵⁸. Also, it is enlisted in threatened and vulnerable species in the essential oil-bearing plants category⁵⁹. A spontaneous reduction of 20% was observed in its population over the last ten years resulting in reported adulteration and substitution of the drug in the markets. Rhizomes of both the Hedychium coronarium and Kaempferia galanga Linn. are sold under the same name Shati due to its morphological similarity with H. spicatum⁶⁰.

 

Phytochemistry:

The rhizomes of Hedychium spicatum shelter various nutritionally and medicinally significant compounds extracted in essential oil and solvent extractions. The rhizome of the plant contained a number of secondary metabolites such as diterpenes, furanoid diterpene, labdane diterpene, polyphenolic compounds, sesquiterpenes, flavanoids, carotenoids, and starch, resins, gums and others (Table-3)⁶¹. The chloroform extract of rhizome was reported to contain 7-hydroxy,6-oxo-7,11,13-labdatrien-16,15-olide, 9-hydroxy,15,16-epoxy-7,11,13(16)14-labdatetraen-6-one, yunnacoronarin A, hedychilactone B, hedychilactone C, chrysin, and teptochrysin compounds⁶². The hexane extract was reported possessing 6-oxo-7,11,13-labdatrien-16,15-olide, 18 spicatanol, spicatanol methyl ether, hedychenone, 7-hydroxy hedychenone, yunnacoronarin D, 7-acetoxy hedychenone, 8 Drimene and hedychia lactone B⁶³. The essential oil hydacheim obtained from the flowers of Hedychium spicatum completely eradicated the growth phase of B. burgdorferi at 0.05% concentration⁶⁴. Suresh et al., 2013 reported a number of new cytotoxic sesquiterpene compounds namely Eudesma-4(15)-ene-β-11diol, crytomeridiol, β-eudesmol, 3-hydroxy-β-eudesmol, mucrolidin, oplapanone, α-terpineol, elemol, dehydrocarissone, Δ7β-eudesmol, Opladiol, hydroxycryptomeridiol, β-caryophyllene oxide, coniferaldehyde and ethylferulate⁶⁵.

 

Table 3: The phytoconstituents reported in Hedychium spicatum rhizome

 

The Hedychium spicatum being a vulnerable species also possessed an essential volatile oil content of about 0.06 to 6.12% and 88 components identified and reported in the rhizome²². Various constituents like α- and β-Pinene, linalool, 10-epi-γ-eudesmol and β-slinene were found in significant quantity in its aromatic oil with 1, 8-cineole (27–75%) reported as its major component.

 

The α-pinene and β-pinene was reported in the range of 0.10-4.50% and 0.13-3.80% respectively by most of the authors while Semwal et al. reported a maximum of 9.12% (α -pinene) and 9.24% (β -pinene) with 4.0-5.9% of β-pinene by Joshi et al. respectively. Sabinene, Camphene, α -Thujene, myrcene and β-myrecene had been reported in range of 0.10-1.30%, 0.10-0.40%, 0.10-0.58%, 0.10-2.50% and 0.10-8.70% respectively^14,72,73.

 

Various other trace constituents of the Hedychium spicatum essential oil i.e. α-phellandrene, 𝛿-2-carene, α-terpinene, γ-terpinene, (E)-β-ocimene, α-cubebene, furfury haxanoate, z-caryophyllene, 4-thujeol, allo-aromadendrene, 9-epi-β-caryophyllene, α & β-himachalene and oplopanone reports presence of only 0.10% in the H.spicatum oil. While a maximum of 0.2% (cis-linalool oxide, trans-linalool oxide, terpinolene, β -elemene, epicubebol, aromaadendrene); 0.3% (𝛿 -terpineol); 0.4% (Germacrene D); 0.5% (8-epi- β -bisabolol, α-copaene); 0.6% (t-elemene, copaene, E-neroliddol); 0.7% (cis-sesquisabinene hydrate, (z)-p-menth-2-en-1-ol, α-(z)-bergamotene); 0.8% (cubebol) and 0.90-1.2% (agarospirol; trans-nerolidol, 𝛿 -Muurolene, 4-terpineol, β-curcumene, epi-α-cadinol; curzerene, α-muurolene, terpinolene ) had been reported respectively^37,73-80.

 

Different constituents of the oil that were present in minor quantity ie., γ -muurolene (0.1-1.5%); eremoligenol (1.3%); sigma-carene (1.40-1.80%); β -terpineol (1.80%); humulene (0.3-2.0%); camphor (0.4-2.16%); hinesol (0.9-2.3%); Borneol (0.1-2.7); humulene epoxide II (0.7-3.1%); caryophyllene oxide (0.23-3.20%); spathulenol (0.6-3.5%); β-farnesene (0.2-3.90%); selinene (4.40%); α-gurjunene (4.51%)and (+)-elemol (4.2-8.5%)⁸¹.

 

However a large variation had been observed in the percentage of essential oil constituents of the rhizome collected from different parts of India (Uttrakhand, Kerala and Himachal Pradesh) being reported by different researchers from year 1977-2016 respectively⁶⁷ i.e., γ-cadinene (0.3-5.40%); β-cadinene (1.74-6.77%);  germacrene-D-4-ol (0.4-6.8%); 1-epi-cubenol (0.5-6.9%); β-phellendrene (0.30-7.0%); p-cymene (0.1-9.60%); T-muurollol (0.0-6.63%); eudesmol (1.6-6.20%); Limonene (0.2-6.42%); 1-8-cineole (5.0-72.10%); Linalool (0.40-25.6%); Terpin-4-ol (0.1-15.20%); α-terpineol (0.10-6.5%); β -caryophyllene (0.1-24.10%); α-selinene (0.1-9.5%); β-selinene (0.9-8.60%); cubenonol (1.65-8.85%); 𝛿 -cadinene (0.9-7.5%); elemol (0.7-16.60%); 10-epi- γ-eudesmol (0.2-13.9%); T-eudesmol (0.0-12.35%);α-cadinol (1.2-11.20%); β-eudesmol (2.2-26.57%); β-eudesmol (0.24-17%) Hedycaryol (1.10-22.38%) and (-)spathulenol (1.67-13.83%) were present in percentage respectively^{37,56,67,73, 74,78}.

 

Further, the variations were observed with respect to other species of Hedychium i.e., coronarium, aurantiacum, ellipticum, venustum and flavescens, along with oil extracted from different parts of H.spicatum plant respectively^70,73,80. The 1,8-cineole (11.9%) was reported higher in the oil obtained from rhizome compared to leaves while inverse in the case of β-pinene (40% in the leaves)⁸¹. The structures of major bioactive compounds were shown in table 4. These essential oil were extracted with the help of hydrodistilled by using Clevengers' apparatus⁸². The mode of extraction of essential oil were different, a number of secondary metabolites such as terpenes, polyphenols and aroma containing compounds would be present⁸³.

 

Pharmacological activities:

Anti-histaminic activity and bronchodilator effect:

The Bharangyadi is composed of Bharangi (Clerodendrum serratum), Sati (Hedychium spicatum) and Pushkarmoola (Inula racemosa) as main herbs was used and the hydroalcoholic extract was used at different doses for the evaluation of the antihistaminic activity. In-vivo histamine-induced bronchospasm model showed 27.8% and 36.1% increase in pre-convulsive time at 200 and 500mg/kg dose respectively. Further in-vitro histamine-induced guinea pig ileum contraction bioassay revealed that the hydro-ethanolic extract of bharangyadi showed maximum inhibition at the 50mg dose of extract when the maximum dose of histamine was used. The standard dexchlorpheniramine showed 19.8% of inhibition of smooth muscle contraction as compared to the bharangyadi extract at 50mg showed an equivalent amount of 15.7% of inhibition of smooth muscle contraction, causing the drug to have a preventative type of antagonism. In continuation of above, the mast cell degranulation studies were carried out in rat mesenteric mast cells where ketotifen was kept as a standard mast cell stabilizing agent. The percentage inhibition of mast cell degranulation of bharangyadi at 500 and 1000µg/ml was found to be 54.67% and 58.83% as compared to standard with a significant reduction of 30.26%. Thus concluded that the polyherbal formulation might act via phospholipase C activation which in turn generates IP₃ (inositol 1, 4, 5-triphosphate) that triggers the release of calcium ions from sarcoplasmic reticulum⁸⁴.

 

Table 4: Major bioactive constituents of Hedychium spicatum.

 

Another clinical study in 1975 reported in 25 patients with 10mg powdered rhizome of plant taken daily was found to reduce recurrent episodes of bronchial asthma. The bronchi congestion was eliminated completely in 36% of patients after 4 weeks of administration with a 20% increase in vital capacity ⁸⁵. Later on, the patients with the pulmonary disease were treated with powder of rhizome at a dose of 6mg twice a day, continued atleast for 4 weeks. The patients’ blood report showed a reduction in inflammatory cell i.e. eosinophils count by 60.54% after treatment ⁸⁶.

 

The rhizome aqueous and ethanolic extracts were also evaluated for an anti-histaminic activity where guinea pigs were used as experimental animals. The extract at 100, 200 and 400mg/kg were administered daily for the 7 days. The increase in pre-convulsive time was observed by 75.1 and 65.1% in aqueous and ethanolic extracts as compared to the standard chlorpheniramine (2mg/kg) with a 71.3% increase. Thereby both the extracts showed significant inhibition of histamine release from mast cells in experimental animals ⁸⁷. However the Zingiberaceae family plants are often reported to cause hepatotoxicity at high doses, so avoided in an individual with hepatic failure ⁸⁸.

 

Anti-inflammatory activity:

Srimal et al., 1984 reported that the alcoholic extract of Hedychium spicatum rhizome possessed anti-inflammatory activity with the help of carrageenan-induced hind paw oedema model in which indomethacin and phenylbutazone were taken as a reference compounds in mice and rats respectively. The hexane extract showed significant activity of 42.16% in mice and 27.2% in rats as compared to indomethacin (2mg/kg) with 37% in mice and phenylbutazone (30mg/kg) with 27.2% in rats. Another cotton pellet granuloma formation model revealed that the benzene and hexane extract (200mg/kg) of rhizome showed a reduction of granuloma formation by 8 and 5% respectively as compared to phenylbutazone with 27% granuloma reduction ⁸⁹.

 

In another experiment model, the tween-80 was used as a vehicle for the alcoholic extract to be administered in experimental animals. The carrageenan-induced rat paw oedema model revealed that the alcoholic extract (30mg/kg) showed a marked reduction of 64.2% of percent inhibition as compared to acetylsalicylic acid with 49.1% inhibition. The hedychinone was the compound reported to be responsible for the anti-inflammatory activity.

 

The anti-inflammatory activities of ethanolic and aqueous extract of Hedychium spicatum rhizome part were used for evaluation of the anti-inflammatory activity. The respective extracts were suspended in 1% carboxymethyl cellulose solution at 200mg/kg dosage and indomethacin (10mg/kg) was taken as a standard drug in the experimental model using plethysmometer apparatus by mercury displacement method. The percentage inhibitions in paw oedema volume in the aqueous and ethanolic extract were found to be 28.10% and 25.62% as compared to the indomethacin with 41.32% inhibition. Further analgesic effect was analysed via tail-flick latency model, the percentage increase in latency period of tail-flick in aqueous and ethanolic extract-treated rats were found to be of 52.9% and 54.1% increase as compared to standard indomethacin with 68% increase. The authors concluded that the aqueous extract of the plant was found to exhibit anti-inflammatory activity which could counteract respiratory problems such as asthma ⁸⁷.

 

Tandan et al., 1997 reported that the different fractions of Hedychium spicatum also possessed analgesic activity. The acetic acid-induced writhing assay in mice and Randall-Selitt assay in rats were conducted and showed significant results in hexane and benzene extract at 284.53 and 93.28mg/kg respectively. The hot plate latency test revealed that the extracts did not make any changes in reaction time to thermal stimuli suggesting the lack of central analgesic activity of Hedychium spicatum. Further, the plant extract were evaluated for peripheral analgesic activity by Randall–Sellitt assay, the ethanolic extract (300mg/kg) showed a decrease in pain threshold by 34.32% as compared to aspirin by 70.35% at the same dosage ⁶⁶.

 

Anti-oxidant activity:

The Hedychium spicatum consisted of essential oil contents and the alcoholic extract of rhizome was reported to contain strong anti-oxidant properties. This was evaluated by using free radical scavenging, chelating and reducing properties. The phenolics compounds such as β-sitosterol, lupeol, stigmasterol-D-glucoside and β-sitosterol-D-glucoside present in the methanolic extract would be the responsible factor for reducing the oxidative stress induced by free radical generation ^{90, 91}. The ethyl p-methoxycinnamate (68%); limonene, β-phellandrene, p-cymene, linalool, β-terpineol, β-caryophyllene, ethyl cinnamate (10%), d-sabinene (4%), 1,4-cineole (6%), sesquiterpenes (5.5%) and sesquiterpene alcohol (4.7%) were the major phytoconstituents present in the volatile oil of Hedychium spicatum ⁹².

 

Anti-diabetic activity:

The ethanolic extract of the plant was evaluated for hypoglycaemic and nephroprotective activity. The oral glucose tolerance test revealed that the group containing 500mg/kg was found to normalise the glycaemic index as compared to the standard methformin. Further, alpha-amylase inhibitory test results revealed that the ethanolic extract had IC₅₀ value of 54µg/ml as compared with the standard acarbose with IC₅₀ of 40µg/ml. Subsequently, the various biochemical parameter including blood urea nitrogen (BUN), creatinine, urinary albumin, and total lipid profile was evaluated after 40 days of the experiment. The serum cholesterol and other lipid levels were found to increase in diabetic rats whereas the high-density lipoproteins were decreased in diabetic rats. The grouped rats treated with 500mg/kg showed significant results as compared to the standard group treated with methformin. The superoxide dismutase, malondialdehyde, glutathione and catalase were found to decrease in diabetic rats as compared to control. Thereby they concluded that the plant extract would alleviate the hyperglycaemic levels. The kidneys of rats were examined under the microscope to check the pathological status in rats with the prolonged diabetic state. Here authors concluded that the groups treated with 500mg/kg dosage and standard were found to have safe glomeruli, with oval-shaped cells, granular cytoplasm with regenerated cell walls, thereby the rhizome ethanolic extract after defatted with petroleum ether was found to be nephroprotective ⁹³.

 

Alpha-glucosidase inhibitor activity:

The phytochemical investigation of hyperglycaemic rhizome extract revealed that the spicatanol compound showed significant blood glucose level reduction via inhibition of α-glucosidase enzyme. The compound spicatanol showed 89.5% of enzyme inhibition with IC₅₀ value 34.1µM ⁶³. Thereby concluded that the α, β-unsaturated γ-lactone and furan ring in diterpenes were the responsible moieties for α-glucosidase enzyme inhibition, subsequently lowered the absorption of carbohydrates in the intestine and proved to be anti-hyperglycaemic agent ⁹⁴.

 

Nootropic activity:

The n-butanol fractional extract was evaluated in mice for cognitive performance by the elevated plus-maze and a double unit mirrored chamber test was carried out. The n-butanol extract (30mg/kg) showed significant enhancement in memory restoration performance of mice. Thereby concluded that the Hedychium spicatum would be used in dementia-associated debilitating diseases i.e. Alzheimer, Parkinson and other central nervous diseases ⁹⁵.

 

Cardioprotective activity:

The benzene and hexane extract of Hedychium spicatum was found to be cardioprotective in nature. The benzene extract (10, 25mg/kg) was administered intravenously in cats. The blood pressure was found to be reduced by 50mm of Hg in 30 minutes whereas the hexane extract lowered the blood pressure by 80 mm of Hg for 16 minutes followed by hypotension. The adrenaline, acetylcholine, histamine and isoprenaline showed no change in either extract administration⁸⁹.

 

In-vitro cytotoxic activity:

Mishra et al., 2015 conducted in-vitro cytotoxic activities of essential oil samples collected from the western Himalayan region and evaluated at different concentrations (10, 25 and 50µg/ml) of Hedychium spicatum four samples against seven human cancer cell lines (A549, DLD-1, SW620, MCF-7, FaDu, MDA-MB-231 and HeLa cancer cell lines. The IC₅₀ value of inhibiting cell growth lied in between 26.77 and 94.33µg/ml. The fourth sample containing major monoterpene alcohol, 1,8-cineole showed significant cytotoxic activity at 50µg/ml as compared to others. Along with this authors identified 1,8-cineol, α-cadinol, cubenol, β-eudesmol as main volatile components via GC-MS analysis⁷⁴.

 

The chloroform extract of hedychium spicatum rhizomes was subjected to isolation of sesquiterpenes where compound showed significant cytotoxic activity against cancer cell lines ⁶⁵.

 

Further Reddy et al., 2009 found two new labdane diterpenes (7-hydroxy hydichinal and spicatanoic acid) both structural analogs that possessed cytotoxic activity when evaluated against cancer cell lines. The human acute monocytic leukemia (THP-1), human promyelocytic leukemia (HL-60), human malignant melanoma (A-375) and human lung carcinoma (A-549), and etoposide as standard were screened using MTT assay. The 7-hydroxy hydichinal was found to be more cytotoxic as compared to spicatanoic acid as the IC₅₀ value of the first compound ranged from 14.14 to 36.56µg/ml. The authors also concluded that the furan ring and the hydroxyl group at the seventh position would be the responsible factor for anti-cancer activity^{68, 96}.

 

Hair loss prevention activity:

The hexane extract of hedychium spicatum rhizome showed a 33% increase in hair growth time whereas the minoxidil, used as standard showed a 47% decrease in hair growth time. The active compounds responsible for hair promotion were not yet reported⁹⁷.

 

Anti-helminthic activity:

The in-vitro antihelminthic activity was carried out in adult Indian earthworms, Pheretima posthuma using ethanolic rhizomatous extract of Hedychium spicatum and Zingiber zerumbet as test extracts and albendazole as a standard compound at 25, 50 and 100mg/ml dosage. The least death time for ethanolic extracts of Hedychium spicatum and Zingiber zerumbet were found to be 96.66 ± 3.266 min and 76.2 ± 1.75 min as compared to reference albendazole with a death time of 73.83 ± 4.167 min at 100mg/ml. Therefore authors concluded that the Hedychium spicatum ethanolic extract showed anti-helminthic activity but little significantly than the Zingiber zerumbet ethanolic extract ⁹⁸. In another study, the aqueous and methanolic extracts were also evaluated for the anti-helminthic activity where the piperazine citrate was taken as a reference compound. The methanolic extract showed significant activity than the piperazine citrate whereas the aqueous extract did not possess any anti-helminthic activity at all ^{56, 98, 99}.

 

In-vitro pediculicidal activity:

The Hedychium spicatum derived essential oil was tested for the in-vitro pediculicidal activity where lice were collected from the infested host and placed on the Whatman filter paper in the Petri dishes. The essential oil was prepared in coconut oil with 1, 2 and 5% concentrations. The 10 lice were kept in each Petri dish and after treatment, they were observed for 120 minutes continuously under a dissection microscope. There was no movement observed in lice after 30 minutes in 2% and 5% treated groups whereas after 120 minutes 95% mortality was seen in 1% treated groups. The permethrin already synthetically derived marketed preparation was found to possessed 79% of mortality after 120 minutes. Therefore, authors concluded that the essential oil could be the substitute for synthetic preparation acting as significant pediculicidal agents¹⁰⁰.

 

Anti-microbial activity:

The plant various extracts were screened for antibacterial and antifungal activity against gram-positive and negative bacterial culture strains including Escherichia coli, Pseudomonas aeruginosa and Candida albicans. The Hedychium spicatum petroleum ether, benzene, ethylacetate, chloroform, acetone, ethanol extract and essential oil were used in the concentration of 20mg/disc and 500µg/ml, where the pet ether and essential oil containing dish was found to have significant antimicrobial activity as compared to standard ¹⁰¹.

 

Patents:

The Hedychium spicatum plant leaves, stem and mostly rhizome were used to extract valuable medicinal compound that was explored in the pharmaceutical market. The compounds were natural in origin, therefore it counterpace the risk/benefit ratio. The n-hexane extract was used therapeutically as it contained a number of furanoid diterpenes, ethyl p-methoxycinnamate, cinnabloc, α-pinene and β-pinene compounds responsible for various pharmacological activities such as anti-inflammatory, analgesic, anti-anxiety behavior and anti-helminthic activity. The Hedychium spicatum containing ethyl p-methoxycinnamate as an active ingredient was used as an anti-helminthic agent. The topical cream containing 10% of HS oil exhibited anti-dermatophytic and melanogenesis inhibiting activity. The anti-melanogenasis activity might be due to Tumor Necrosis Factor-α (TNF-α) inhibition and nitrous oxide inhibition. Moreover, the composition possessed deodorant properties too ¹⁰². The amount of the H. spicatum Linn., root extract, concentrate or active ingredient was preferably in the range of about 0.0001% to about 20%, more preferably about 0.001% to 10%, and most preferably 0.01% to about 5% were used for the treat baldness and increased the volume of hair desirably ¹⁰³. In a clinical study of fifteen patients having tropical pulmonary eosinophilia were given dried powdered rhizomes of Hedychium spicatum at a dose of 12grams twice daily for four weeks. This resulted in a 60.54% reduction in total absolute eosinophil count, which was found to be statistically significant. Further, 86.6% of the patients showed signs of improvement when assessed for symptoms like dyspnoea, cough with expectoration, dry cough, palpitation, headache and fever. The results were found to be better when compared to the other group of patients treated with Rasamanikya and Kanakasava ¹⁰⁴. Our findings indicate that the Hedychium spicatum extract and essential oil possess a number of the therapeutic potentials and may be useful in the management of chronic pain, diabetes, dermal allergies and insomnia disorders. A number of patents and ethnomedicinal uses of Hedychium spicatum (Zingiberaceae) were listed in table 5.

 

Table 5: the list of Hedychium spicatum patents evaluating the significant therapeutic properties.

 

DISCUSSION:

The available scientific data supports that the Hedychium spicatum is a highly medicinal, essential oil containing herb endemic to Madagascar, native to Central and South eastern Asia with origination and diversification in S. China and North Eastern India.

 

The species has been explored by various researchers in last 4-5 decades with respect to pharmacognosy, phytochemistry, traditional uses and pharmacological therapeutics along with various in-vitro, in-vivo and clinical studies. Morphologically, the species is an ornamental plant with beautiful flowers and diverse foliage; however pharmacognostically, its camphoraceous, scented rhizome has been reported as ethno-medicinally useful in treatment of various pain, inflammations, asthma, foul breath, fever, vomiting, diarrhoea, bronchitis, hiccough and blood disorders as mentioned in various classical texts of the Indian, Tibetian, Chinese and Unani origin. It is one among popular the Ayurvedic plant used by various famous Indian practioners like Charaka, Sushruta in their formulation since ancient times and has now been commercially sold throughout India¹¹⁶. Although contemporary research related to the species is quite promising however sometimes it is too preliminary and basic which unable to explain molecular mechanisms behind pharmacological effects of the species.

 

It forms an important part of different classical and commercial polyherbal formulations in treating anti-inflammatory, cardio vascular and respiratory disorders. Both essential oil and extracts of H. spicatum were found pharmacologically active. The essential oil from the rhizome has reported pediculicidal, anti-microbial, anti-oxidant and anti-cancerous activity while anti-histaminic, bronchodilatory and anti-inflammatory activity has been shown by both alcoholic and aqueous extracts respectively. However anti-oxidant, anti-diabetic activity, anti-helminthic activity was reported in alcoholic extracts only with nootropic, cardioprotective, anti-hair loss, anti-microbial activity with significant results in n-butanol, benzene, hexane and pet ether extracts respectively.

 

The plant reports number of active constituents (multi-constituents) responsible for various pharmacological and clinically proven activities, in both of its essential oil and extracts. The rhizome are medicinally active with 1,8-cineole as major active constituent of essential oil extraction while labdane terpene, hedychinone, polyphenols and terpenoids as major constituents found in the herbal extracts. It was found that essential oil constituents percentage varies with respect to environment ie., altitude, habitat, forest cover and population respectively¹¹⁷.

 

The various literature reviews on Hedychium spicatum, cited the botanical, traditional, ethnomedicinal and pharmacological aspects of the species having diverse uses mentioned in classical texts with elaborated chemical profiling of its essential oil constituents and their percentage in detail^44,48,56,118. It was also found that variations in the content of the species exists with respect to certain phytochemicals, such as polyphenols at different development stages of the species, leading to variations in pharmacological activity, collected from different sites of India i.e., Uttarakhand and Himalayan region^14,15. However information on its metabolic chemistry, specific pharmacological activities and adverse effects of the species (drug safety issues) are scarce.

 

The present review is a summarize form of research work reported on the species till date with additional information related to patents granted for polyherbal formulations containing H. spicatum.

 

Since the plant is multi-constitutional and used in various polyherbal formulations, it is difficult to attribute a particular phytocompound of the herb for a specific property. Also, the reported medicinal property may be due to synergistic effect of existing constituents of the species or formula in multi-herbal composition. In this regard, systemic biology which includes metabolomics study needs to be taken into consideration to infer mechanism of action with respect to specific active constituent responsible for reported activity¹¹⁹.

 

As its rhizomes are highly in demand and being traded in various crude drug markets all over the world, has led to it scarcity, adulteration and use of various allied drugs as its substituent’s in the markets. Also illegal collection and indiscriminate exploitation of the herb for commercial use has been trending these days, thereby dwindling it from its natural habitat rapidly. It was concluded that the plant need to be cultivated at large scale on priority basis to meet the higher trending demand of the species in the market and check its adulteration. Sustainable multiplication of the species may be achieved by adopting appropriate plant breeding methods by identifying genetic variation in traits ^{13, 74, 75, 120}. Also, various propagation techniques such as plant tissue culture, conventional methods can be used for better conservation of the vulnerable species and re-establish this plant in its natural habitat.

 

CONSENT FOR PUBLICATION:

All authors have undersigned the consent for the publication.

 

CONFLICT OF INTEREST:

The authors declare that they no conflicts of interest.

 

Table 6: List of abbreviations

 

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Received on 19.09.2021         Modified on 05.12.2021

Accepted on 18.01.2022       ©A&V Publications All right reserved