Therapeutic attributes of Aromatic Ginger (Kaempferia galanga L.) Introduction:

 

Therapeutic attributes of Aromatic Ginger (Kaempferia galanga L.) 

Introduction:

Currently most of the people living both in developing and developed countries are completely dependent on traditional medical practices for their primary health care needs (Calixo 2005). Several records of such medicinal plants are also issued by different National and International organizations. The therapeutic role of such plants in disease management is still being researched enthusiastically because of their low side effect and affordable properties. Among the list of medicinal herbs and spices issued by International  Organizations, Aromatic Ginger (Kaempferia galanga  L.) is one of the important medicinal herbs which is  still internationally underutilized and comparatively less known to the places other than native places (Nag and Mandal 2015). The plant is native to tropical Asia including Southern China, Thailand, Taiwan, Malaysia, Bangladesh and India (Techaprasan et al. 2010). In native places such plants are widely used as medicinal and edible purposes. Leaves and rhizomes are also used as vegetable and eaten fresh or cooked. Rhizomes are often used as ingredient of a beverage- “Beras Kenchur”. These plants are mainly exploited due to medicinal properties of rhizome. According to IUCN it is critically endangered because of  excess and unscientific collection of rhizome by native peoples. The rhizome of this plant has been used traditionally for the treatment of many ailments and few biological activities have proven its importance (Rajendra et al. 2011). Roots are also used to increase the flavor of cooked foods and also as medicines in some parts of tropical Asia (Ratsch 1998). Different types of preparation based on this plant or its constituents are very popular in Ayurveda, Unani, Homeopathy and even in Modern Medicine for curing different human disorders.

 

Phytochemical Constituents:

Bioactive compounds derived from plants, have enriched the chemical and pharmaceutical sector since long time. Any medicinally recognized plant is characterized by the diversity of chemical and pharmacological constituents. Kaempferia galanga L. has complex of various constituents which are very popular in many countries for disease management. A total of 49 compounds including 05 esters, 15 terpenoids, 02 flavonoids, 03 thiourea derivatives, 09 polysaccharides, 06 diarylhaptanoids, 01 phenolic glycoside, 03 phenolic acids, 04 benzoic acids and 01 cyclic lipodepsipeptide have been identified from K. galanga (Kumar 2020).  Rhizomes of the plant have been reported to have different types of volatile oils including ethyl cinnamate, ethyl-p-methoxycinnamate, γ-cadinene, 1,8-cineole, δ-carene, borneol, ethyl-m-methoxycinnamate, camphene, linoleoyl chloride and α-pinene (Kumar 2014). K. galanga  rhizome was found to have secretory sacs containing volatile oil, oleoresin and starch grains which were also found in the parenchyma cells. In addition with  volatile oil it also contain several other compounds like alkaloids, carbohydrates, protein, aminoacids, minerals and fatty substances (Truntiwachwuttikul et al. 1991; Wong et al. 1992).The major chemical constituents of the volatile oil from the dried rhizome of Kaempferia galanga are ethyl-p-methoxycinnamate (31.77%), methyl cinnamate (23.23%), carvone (11.13%), eucalyptol (9.59%) and pentadecane (6.41%), respectively (Dash et al. 2014; Munda et al. 2018). Major biological activity of the essential oil is mostly due to these major compounds. Though some of the minor components are also responsible for its pharmaceutical activity, not much emphasize or effort has been put on these minor components. Among the minor constituents of the rhizome some have gained attention of present scientists. These are cineol, borneol, 3-carene, camphene, kaempferol, cinnamaldehyde, p-methoxycinnamic acid, and ethyl cinnamate (Dash et al. 2014).  In addition the plant  retains huge amount of minerals like potassium, phosphorous and magnesium in higher amount with the appreciable quantity of iron, manganese, zinc, cobalt, and nickel (Srivastava et al. 2019).

 

About 98.98% of essential oil constituents have been isolated and identified with only 1.11% constituents that are still unknown (Huang et al. 2008). The most abundant essential oil constituents include propanoic acid, pentadecane, ethyl-p-methoxycinnamate. Other constituents include 1,8-cineol, undecanone, isopropyl cinnamate, dicyclohexyl propanedinitrile, dipentene dioxide, 9-hydroxy, 2-nonanone, 2,7- octadiene-1-yl acetate, ethyl cyclohexyl acetate, cis-11- tetradecenyl acetate, 2-heptadecanone, 4-methyl isopulegone, camphidine, trans,trans-octa-2, 4-dieny acetate, 10 undecyn-1-ol, 3,7-dimethoxycoumarin, delta- 3-carene, alpha pinene, camphene, borneol, cymene, alphaterpineol, alpha gurjunene, germacrenes, cadinenes, caryophyllenes, luteolin and apigenin (Khare et al. 2004, Othman et al. 2006, Sutthanont et al. 2010, Koh et al. 2009). Extract and purified compounds of the plant are effectively provide health benefits to human.

Table 1. Important phytoconstituents of Kaempferia galangal

 

Sl No.	Name	Structure
1.	Ethyl cinnamate
2.	Ethyl-p-methoxycinnamate
3.	Ethyl-m-methoxycinnamate
4.	Methyl cinnamate
5	Carvone
6.	Eucalyptol
7	Borneol
8.	Kaempferol
9.	Dipentene dioxide
10.	2-nonanone
11.	Cymene
12.	Alpha gurjunene

 

 

 

Mechanism of action of active compounds:

Kaempferia galanga L. shows therapeutic roles in health management due to its various phytoconstituents. But the actual molecular mechanisms in the prevention of pathogenesis is still not understood properly. Some  researchers  considered that  the therapeutic implication of the  plant is due to the rich source antimicrobial substances and other active compounds. The rhizomes of the plant are widely used in East Asia for a wide range of medicinal applications. Leaves and flowers of K. galanga contain flavonoids. For aroma and flavour these components are used in food stuffs and beverages. Leaves are also used as a perfume in washing hairs. The leaves possess antioxidant, antinociceptive and anti-inflammatory activities that help in treatment of mouth ulcers and headaches (Sulaiman et al. 2008; Chan et al. 2009). The ashes of leaves are rubbed on swollen breasts after childbirth while fresh leaves are chewed for relieving coughs (Sulaiman et al. 2008). The leaves and rhizomes are used in cosmetics and herbal powders (Hali et al. 2006). The plant is also effectively used in aroma therapy and forms one of the ingredients in pain relief ayurvedic massage blends (Huang et al. 2008).

 

Therapeutic uses:

Kaempferia galanga L. is one of the famous plant species having medicinal efficacy. Various investigators have confirmed the biological and pharmacological attributes of different bioactive compounds of the plant. Several scientific investigations also examined antibiotic, antimicrobial, antidiabetic, antidiarrheic, antispasmodic, and sedative effects, as well as anti cancer activities of the plant species. Active compounds of the plant play role in diseases via activation of antioxidant enzymes, inactivation of  toxic substance, lethal and inhibitory activity of growth and development of pathogens etc through the regulation of cytological pathways. Indigenous medicinal practitioners use the different parts of the plant Kaempferia galanga L. for the treatment of  various common health disorders like fever, common cold, digestion problem, wound, pain etc. The rhizome has immense importance in the traditional health care system as a carminative, cholera, anti-inflammatory, abdominal pain, dyspepsia, and stomachic as well as in the diseases of coughs, pectoral affections, and stoppage of the nasal blocks (Dash et al. 2014).  Extract of rhizome of the plant is frequently used abdominal pain in women (Mokkhasmit et al. 1971; Hirschhorn 1983; Tewtrakul et al. 2005). It is also useful to get rid of dirty blood and get through periods smoothly (Kanjanapothi  et al. 2004; Samodra and Febrina 2019). The rhizomes and root stocks are good for dyspepsia, leprosy, skin diseases, rheumatism, asthma etc (Kirtikar and Basu 1996). The leaves possess antioxidant, antinociceptive and anti-inflammatory activities that help in treatment of mouth ulcers and headaches (Sulaiman et al. 2008; Chan et al. 2009).

 

Anti-oxidant activity:

Antioxidants are the molecules which reduce or inhibit oxidation reaction by terminating free radicals which damage cells in  various ways. Such damages are responsible for several diseases and physiological abnormality in humans. Neutralization of such free radical activity is one of the prime step in prevention of diseases. The antioxidant activity  of K. galanga is directly correlated to the phenolic content, carotenoids and some vitamins like vitamin C, vitamin E present in plant extracts (Kumar 2020). Rhizome extract in methanol exhibited a concentration-dependent antioxidant activity in 1,1-Diphenyl-2-picrylhydrazyl assay (DPPH), 2,2′-Azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) assay (ABTS), and nitric oxide (NO) radical scavenging assays (Ali et al. 2018). The whole plant extracts have weak or moderate  antioxidant activity (Chan et al. 2008; Mekseepralard et al. 2010). This antioxidant activity is mainly due to the total phenolic content and flavonoid including Luteolin and Epigenin (Mustafa et al. 2010). A study was carried out to evaluate antioxidant activities of hydoethanolic extract of K. galanga and result of the study confirmed the presence of some phenol antioxidants namely Genistein, Ferulic acid, Coumaric acid and Butein (Kaushita et al. 2015).

 

Anticancer and Anti tumour Activity:

The plant has tremendous potential and has the capability of antitumor activity. Several researchers have isolated some anticarcinogenic  compounds from K. galanga  like, cis ethyl-p-methoxycinnamate,  trans ethyl-p-methoxycinnamate (Xue et al. 2002). Yang et al. (2008) isolated a water soluble acidic polysachharide from rhizome of the plant which has antitumor activity on H22 tumor-bearing mice. Ethanolic extract of  K. galanga had cytotoxic activity against human Hela cancer cell line. Ethyl-p-methoxycinnamate (EPMC) of rhizome shows moderate cytotoxic activity against human Cholangiocarcinoma (CCA) tumor (CL-6) cell line (Amuamuta et al. 2017). Some workers confirmed that different extract of the plant have antiproliferative activity on organ specific cancer cell line in a dose dependent manner (Srivastava et al. 2019). Methanolic extract of rhizome has been found to induce Ehrlich ascites carcinoma (EAC) cell death in a dose dependent manner (Ali et al. 2018). Some researchers confirmed that extract of the plant possesses inhibitory effect on tumour promoting  arrange of neoplasia and hence considered as antineoplastic (Vimala et al. 1990). The crude extract of rhizome and some progressive extracts like petroleum ether, ethyl acetic acid derivation and ethanol are assessed by circuitious immunofluorescent assay and Westernblot and result showed that it has fractional or inhibitory effect on tumour promoting stage (Vimala et al. 1990). Other results also confirmed anticancerous activity of  K. galanga  against different cancerous cells like DU145, PA1, SW620, B16F10  cardiac fibroblast (cell line HCF-7), human T cell leukemia (HT-29 cell line)  etc (Kirana et al. 2003). In a study it has been  reported that a flavonoid Kaempferol play a significant role apoptosis in human lung non small carcinoma H460 cell growth by activation of antoxidant enzymes (Leung et al. 2007). However many others studies revealed that Kaempferol significantly inhibit growth of cancer cell by signal transduction pathway (Casagrande and Darbon 2001; Bestwick et al. 2007). It is also reported that Kaempferol has the ability to induce apoptosis in various cells like leukemia cells, lung cancer cells, glioblastoma etc (Nguyen et al. 2003 (a); Nguyen et al. 2003 (b); Chen et al. 2005; Leung et al. 2007). Another study confirmed that Kaempferol can inhibit proliferation of human breast carcinoma MDA- MB-453 cells by arresting G₂/M phase of cell cycle via modulation of P53 pathway (Choi et al. 2008). Similar mechanism is also reported for GC cell line treated with Kaempferol (Song et al. 2015). Lee et al. (2015)  certified that Kaempferol can inhibit migratory activity of pancreatic cancer cell through the apoptosis in vitro in a dose dependent manner.

 

Antimicrobial Effect:

Different antimicrobial bioactive compounds are present in different part of the  plant. Acetone, petroleum ether, chloroform and methyl alcohol extracts  of the K. galanga have moderate antibacterial activity against both Gram positive and Gram negative bacteria.  Ethyl-P methoxycinamate  isolated from K. galanga essential oil has diverse anti-microbial activity against Mycobacterium tuberculosis, Staphylococcus aureus, Streptococcus pyogenes, Salmonella typhyi, Seratia marcescens, Vibrio cholerae, Vibrio parahaemolyticus, Enterococcus faecalis and Pseudomonas aeruginosa (Tewtrakul and Subhadhirasakul 2007; Techaprasan et al. 2010; Takaishi et al. 2012). Rhizome extract of the plant is useful to stop the viral activity. A rhizomes extract of K. galanga inhibits Epstein–Barr virus with no cytotoxic  effect in Raji cells (Vimala 1999). It also has nematocidal  and hatching inhibition activity. Crude extracts has shown considerable nematicidal activity against Meloidogyne incognita and Bursaphelenchus xylophillus (In-Ho et al. 2006; Hong et al. 2010; Tae-Kyun et al. 2010). K. galanga also exhibited amoebicidal activity against three species of Acanthamoeba: A. culbertsoni, A. castellanii and A. polyphaga, the caus­ative agents of granulomatous amoebic encephalitis and amoebic keratitis (Chu et al. 1998). The plant induced encystment of all three species of Acanthamoeba and was not lytic for normal macrophage cultures.

 

Jantan et al. (2003) conducted an experiment to evaluate  the in-vitro antifungal activity of essential oil of K. galanga rhizome using broth micro-dilution and disc gel diffusion methods against five dermatophytes viz. Trichophyton mentagrophytes, T. rubrum, Microsporum canis, M. nanum and Epidermophyton floccosum, three filamentous fungi viz. Aspergillus niger, A. fumigates and Mucor sp., and five strains of yeast namely Saccharomyces cerevisiae, Cryptococcus neoformans, Candida albicans, Candida tropicalis and Torulopsis glabrata and showed that essential oil is effective against dermatophytes but ineffective against yeasts.

 

Antidiabetic activity:

K. galanga  has been reported for its antidiabetic activity. Diabetes is gradually becoming a serious threat to human health in all parts of the world. A diabetic patient suffers from high glucose level in blood and high blood pressure. Normally it is controlled by a pancreatic hormone Insulin. It was believed that flavonoids of K. galanga  can reduce blood glucose levels in certain doses. In several experiments  on animal model it was confirmed that rhizome of the plant can decrease glucose level in blood. Latifah (2014) proved that K. galanga  can decrease blood glucose levels  body weight of diabetic mice and also improve pancreatic Langerhans islands. It is also effective to reduce blood cholesterol and LDL levels (Handayani 2015). Higher concentration of glucose causes a number of eye diseases and retinal injury. Recently it was proved that Kaempferol protected  retinal ganglion cells from high-glucose- induced injury of retina (Zhao et al. 2019). According to this research by controlling extracellular signal regulated kinase 1/2 (ERK 1/2) phosphorylation Kaempferol regulate (Vasohibin-1) VASH 1, which in turn may protect retinal injury as well as treat diabetic retinopathy.

 

Anti-inflammation:

Inflammation is simply defined as the body’s response to tissue damage which is always followed by repair. On the other hand allergy is an exaggerated immune response to contact with a foreign substance, which may be something ingested, inhaled or touched. Inflammation is linked to certain diseases that can be found in the community, usually characterized by swelling, pain, redness, and heat. The inflammation can be caused by a normal protective response to tissue injury from physical trauma, hazardous chemicals, or microbiological agents. Samodra and Febrina,  (2019) showed that the ethanol extract of K. galanga  rhizome  had anti-inflammatory activity at all dose levels.  In another experiment it was found that 600 mg/kg and 1200 mg/kg dosed of alcoholic extracts of the rhizome exhibited significant anti-inflammatory activity in carrageenan model and cotton pellet granuloma model and significant analgesic activity in tail flick model and hot plate model (Vittalrao et al. 2011). Flavonoid compounds found in K. galanga are immunomodulated against microbial abilities of neutrophil cells (Revilla et al. 2008). Another finding has confirmed that leaves of the plant also showed remarkable anti-inflamatory and antinociceptive effect in rat in a dose dependent manner (Sulaiman et al. 2008). K. galangal rhizome extract exhibited antinociceptive activity in rat that was weaker than morphine but stronger than aspirin (Elshamy et al. 2019).  A finding revealed that the extract of the plant inhibits inflammation by suppressing interleukin-1, Tumour Necrosis Factor-α, and angiogenesis by blocking endothelial function (Umar et al. 2014). A double blind randomized clinical trial revealed that extract of K. galanga has the equal effectiveness as meloxicam in reducing pain, stiffness in patient with knee osteoarthritis (Syahruddin et al. 2017). Many researchers of present era reported the antiallergic effect. It has been found that various composition of  K. galanga extracts  have great array of potent constituents, which can effectively inhibit  allergy and inflammation by suppressing the production of granulation tissue in a rat model  Kaempferia galanga rhizome water extract at 100 pg/ml elicited 75 % anti-allergic activity as determined by the percent inhibition of the release of p-hexosaminidase from rat basophilic leukaemia RBL-2H3 cells, whereas the ethanol extract elicited 54.5 % and the volatile oil 57.8 % at the same concentration (Tewtrakul and Subhadhirasakul 2007).

 

Anti hypertensive Activity:

The chloroform extract of K. galanga exhibited vasorelaxant effects on the smooth muscles of the rat aorta (Mustafa et al. 1996). A result of an experiment confirmed that extract K. galanga  inhibit calcium influx into vesicular cells of  rat just after  5-10 min of injecting it (Othman et al. 2002).  In this experiment it was shown that intravenous administration of K. galanga extract induced a dose dependent reduction of basal mean arterial pressure (MAP) in the anaesthetized rat. According to the study ethyl cinnamate isolated from the rhizome exhibited vasorelaxant effect by inhibiting the tonic contraction induced by high K⁺ ion and phenylephrine in a concentration dependent manner. It inhibited the tonic contractions induced by high K⁺ and phenylephrine in a concentration- dependent manner, with respective IC₅₀ values of 0.30 mM and 0.38 mM (Othman et al. 2006). The relaxant effect against phenylephrine-induced contractions was greater in the presence of endothelium. It was found that the inhibitory effects of ethyl cinna­mate may involve inhibition of Ca²⁺ influx into vascular cells and release of nitric oxide (NO) and prostacyclin from the endothelial cells. K. galanga rhizome extract also exhibited potent brine shrimp lethality bioactivity with an ED₅₀ value of 7.92 pg/ ml (Othman et al. 2006). Extracts of the rhizome also exhibit measurable antihypertensive activity (Zakaria 1994).

 

Wound healing Activity

Many plants have wound healing activity. It has been suggested that certain compounds in the Kaempfiera galanga L. plants have very effective wound healing activities. It is traditionally believed that chemical constituents of rhizhome and leaves retain some phytoconstituents having wound healing activities. Tara et al. (2006) showed that K. galanga significantly reduced the time needed for epithelialisation. Some researchers reported that alcoholic extract of the plant have appreciable wound healing effect on incision, excision and dead space wound with a notable reversal of dexamethasone induced delay in epithelialisation and wound breaking strength (Tara et al. 2006; Koh 2009).

 

Sedative activity

Plants or their isolated compounds are in the regular practice to treat as sedative agents. The plant Kaempferia galanga has been traditionally used to help restlessness, stress, anxiety, depression etc., in several tropical regions. It also has a long history of fragrance use for improving sleep or minimizing stressful situations (Huang et al., 2008). The rhizomes of the plant, which contains essential oils, have been traditionally used in treatment of  headache and toothache (Kanjanapothi et al., 2004). Different extracts of K. galanga exhibited significant dose dependent and long lasting sedative effect due to different constituents of the plant (Ali et al. 2015). In some countries like Thailand dried rhizome has been used as stimulant of Central Nervous System (Mokkhasmit et al. 1971). Inhalation of hexane extract of K.galanga at doses 1.5 and 10 mg showed a notable reduction of  locomotor activity indicating considerable sedative and relaxant effects (Huang et al. 2008). In a study it was shown that inhalation of  hexane extract of the plant  results gradual drop of locomotor activity in rat and it is also confirmed that the sedative activity is due to ethyl trans-p-methoxycinamate and ethyl-cinnamate  (Umar et al. 2011). Ethyl trans-p-methoxycinamate and ethyl-cinnamate possess sedative effect at 0.0014 mg and 0.0012 mg, respectively (Huang 2008). Ethyl trans-p-methoxycinamate acts as inhibitor of Monoamine Oxidase , which is involved in the degradation process for various monamine released by neurons and glia cell. Ethyl trans-p-methoxycinamate also exhibited competitive inhibition with respect to benzylamine (Noro et al. 1983). Another study demonstrated that different extracts of the plant K. galanga possess potent Central Nervous System depressant activity in thiopental sodium induced sleeping time hole cross and open field model (Ali et al. 2015).

 

Anti-diarrhoeal Activity

Many plants and their ingredients  play a significant role in controlling diarrhoea, which is a very common health problem of human beings. Mostly it is caused by an infection in gastrointestinal tract but some time it is caused due impaired nutrient absorption, impaired digestive function, endocrinal imbalance, drugs or laxative intake etc. Most recent evidences have shown that, the disorder affects almost 3-5 billion people every year and accounts for about 5-6 million deaths among children younger than 5 years of age (Hirudkar et al. 2020). In most part of the tropical region rhizome of the plant K. galanga is widely used as antidiarrhoeal medicines. In an experiment conducted by Ali et al. (2015) it was  confirmed that extract of the rhizome has the power to inhibit the intensity of  castor oil induced diarrhoea of mice.

 

Treatment of Excretory System related disorder:

Medicinal plants and their ingredients play many significant role in protection of renal and urinary system without any adverse complications. A study was performed to investigate diuretic activity of  rhizome-petroleum ether extract of  Kaempferia galanga  L. in rat by Lipschitz method and results confirmed that active constituents of the extract can significantly increase urine volume as well as increase of Sodium and Potassium in urine (Mohamad et al. 2016) . According to many workers the phytochemical content of essential oils such as steroids, triterpinoids and resins contained in Kaempferia galanga rhizome have the potentiality as anti-diuretic activity.

 

Anti-asthma:

Traditionally the rhizome extract of the plant is recommended for the treatment of asthma. Asthma simply refers a heterogeneous disease usually characterized by chronic airways inflammation. The root is used internally to treat asthma and other respiratory diseases. Ethyl cinnamate and ethyl p-methoxy cinnamate (EPMS) from essential oils of the plant are widely used as drug for antiasthma (Sahara 2016).

 

Conclusion:

Since last few decades focus on traditional medicine and medicinal plant has increased in all corners of world. Gradual survey and subsequent research have explored many medicinal plants and some of which are widely used as therapeutic ingredients. Kaempferia galanga is also an important herb with many valuable medicinal properties. The plant has been used as treatments for long time, based on experience and folk remedies and continue to draw wide attention for its role in health protection and treatment of diseases. Now a days the plants K. galanga or aromatic ginger has already gained the acceptances in most of the part of world because of their medicinal activity, odour and tastes. In the present review, while going through the literature, it was observed that there is a great diversity of  high value bioactive compounds in K. galanga. Many experimental studies have demonstrated and proved the therapeutic activity of the plant. The further and advanced study and research could improve and enhance their application in more broader and appropriate range. Due to the presence of wide bioactive compounds, the rhizome and other parts of the plant have vast application but it is also fact that there is a need of more research to characterize the less known or uncommon constituents of the  plant. Therapeutic attributes of the plant is associated with both major and minor bioactive compounds of the plant. Therefore, along with the major components, minor components should also be studied to find out its underlying potent biological activity. In this review we have tried to present the up-to-date information available on the therapeutic attributes of the plant. This review would also provide new perspectives on the research directions towards pharmacologically active natural products and their commercial utilization. Further research is also needed to confirm their activities mentioned in ancient traditional document as well as their safe application on human bodies.

 

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