Medicinal importance of Kaempferia galanga L. (Zingiberaceae): A comprehensive review

Introduction Medicinal plants have long been used for human health needs (1,2). Active compounds derived from medicinal plants are widely utilized to meet the demands of the pharmaceutical industries. Today, people in developing countries still use medicinal plants to treat various diseases (3,4). Each medicinal plant also has a variety of phytochemicals and pharmacological activities (5,6). Kaempferia galanga belonging to the Zingiberaceae family, is one of the potential medicinal plants endemic to India and distributed across Indonesia (7,8), Laos (9), Sri Lanka (10,11), China (12), Malaysia (13,14), Nigeria (15), Thailand (16,17), Bangladesh (18), Japan (19), Sudan (20), and Vietnam (21). In traditional medicine in Asian countries, this plant is widely used by local practitioners (22). Due to overuse of K. galanga, this plant is becoming rare and endangered in Bangladesh and India (18,23). As a medicinal plant, K. galanga is beneficial to treat asthma, hypertension, stomachaches, headaches, rheumatism, toothaches, indigestion, and bacterial infections (24,25). In addition, the dried rhizome part is a valuable cardiotonic and sedative remedy (26). The acetone extract from this plant has activity on the retardation of monoamine oxidase (27). K. galanga rhizome can be used to restore internal heat and improve blood circulation (28). Its powder has benefited as an expectorant to cure cough with phlegm and chest pain (29), while the rhizomes’ essential oil, is able to relieve colds and nasal congestion http://www.herbmedpharmacol.com doi: 10.34172/jhp.2021.32


Introduction
Medicinal plants have long been used for human health needs (1,2). Active compounds derived from medicinal plants are widely utilized to meet the demands of the pharmaceutical industries. Today, people in developing countries still use medicinal plants to treat various diseases (3,4). Each medicinal plant also has a variety of phytochemicals and pharmacological activities (5,6).
Kaempferia galanga belonging to the Zingiberaceae family, is one of the potential medicinal plants endemic to India and distributed across Indonesia (7,8), Laos (9), Sri Lanka (10,11), China (12), Malaysia (13,14), Nigeria (15), Thailand (16,17), Bangladesh (18), Japan (19), Sudan (20), and Vietnam (21). In traditional medicine in Asian countries, this plant is widely used by local practitioners (22). Due to overuse of K. galanga, this plant is becoming rare and endangered in Bangladesh and India (18,23). As a medicinal plant, K. galanga is beneficial to treat asthma, hypertension, stomachaches, headaches, rheumatism, toothaches, indigestion, and bacterial infections (24,25). In addition, the dried rhizome part is a valuable cardiotonic and sedative remedy (26). The acetone extract from this plant has activity on the retardation of monoamine oxidase (27). K. galanga rhizome can be used to restore internal heat and improve blood circulation (28). Its powder has benefited as an expectorant to cure cough with phlegm and chest pain (29), while the rhizomes' essential oil, is able to relieve colds and nasal congestion

Plant description
Kaempferia galanga belongs to the Zingiberaceae family that emerges from a tubed rootstock with fibrous cylindrical roots. Its rhizome has reddish-brown skin and a soft interior that is almost white, while it has 2-5 leaves (8-15 cm) with dark green color spread horizontally, and elliptical to slightly flattened with a circular outline. The blade is often lying flat on the ground, the bottom superficies are hairy with spiders, while the top superficies are smooth (34).
Each plant has 4-15 white flowers, which appear between the leaves with 1-3 cm long lobes and 2-5 cm long tubes. The lip of the flower is wide oval and white or purple in color with purple spots on the base. Each lateral lobe measures about 2-3 cm ×1-2 cm. Stamens have imperfect anthers that are oval to spear-shaped, white in color, 10-12 mm long, and have two lobes strongly attached to bent lobes (34). The morphology of K. galanga can be seen in Figure 1.

Traditional uses
The use of K. galanga as a natural treatment has been a pioneer in the development of new drugs (39). Researchers have attempted to gather information on the use of K. galanga as traditional medicine (6,40,41).
Local tribes in Northeast and South India such as the Kuruma, Manipur, Malayali, Kurichiya, Mullu kuruma, and Meghalaya tribes use the plant to treat several diseases such as ear inflammation in children, indigestion, stomach pain, vomiting of blood, gastroenteritis, whooping cough, tongue blisters in babies, menstrual pain, baldness, intestinal wounds, abortifacient, toothache, rheumatism, flatulence, headaches, mouth sores, dandruff, sore throat, body aches, diarrhea, runny nose, and snake poison antidote (49).

Pharmacological and therapeutic activities
Kaempferia galanga has many pharmacological and therapeutic activities as listed below: Antimicrobial activity The plant's extract contains ethyl-p-methoxycinnamate compounds, which have considerable antimicrobial activities to combat Mycobacterium tuberculosis (16,25) Anthelmintic activity A research evaluated the anthelmintic activity of K. galanga extract at doses of 25, 50 and 100 mg/mL in brine against the Pheretima posthuma earthworm compared to albendazole 10 mg/mL as the standard drug. Mortality occurred in extract consentration of 25, 50, and 100 mg/ mL. The extract at a dose of 25 mg/mL showed a paralytic effect on the worms in approximately 48 minutes and over 80 minutes to die. Meanwhile, at the concentrations of 50 and 100 mg/mL the extract was able to impose paralytic effect followed by death. Thus, K. galanga extract showed dose-dependent anthelmintic activity (52).
Antidengue activity Another extract's compound, cystargamide B, had the inhibitory activity on dengue virus replication in the cell-based virus replication against NS2B/NS3 complex. Protease activity in the presence of cystargamide B (0.194 and 0.149 relative fluorescence units (RFU) per second) at doses of 100 and 200 μg/mL indicated a decrease of 44% and 67%, respectively, in comparison with absent (0.343 and 0.453 RFU per second). Therefore, it is successively proved that the cystargamide B compound derived from K. galanga had inhibitory activity protease of the NS2B/ NS3 complex, thus making it a good candidate for antidengue drugs (53).

Antioxidant activity
The antioxidant activity (51,54) was found in the leaf and rhizome extracts with total phenolic content of 146 mg gallic acid equivalent/100 g and 57 mg gallic acid equivalent/100 g, respectively. Moreover, the antioxidant activities of leaf and rhizome of K. galanga extracts were 77 mg ascorbic acid/100 g and 17 mg ascorbic acid/100 g (54). However, the antioxidant activity decreased by drying with distinct non-thermal and thermal drying methods. However, this reduction was averted if the plant underwent freeze drying (55). Additionally, the antioxidant activity of K. galanga extract might be influenced by the total content of flavonoids, phenolics, apigenin, and luteolin (46).
Anti-inflammatory activity Cyclohexane, ethyl acetate, chloroform, and diarylheptanoids derived from K. galanga extract indicated retardation of lipopolysaccharide-induced nitric oxide in 264.7 RAW macrophages compared to indomethacin (48). The compounds from K. galanga have significant anti-inflammatory activity based on the expression of the mRNA nitric oxide synthase gene, accentuation of nitric oxide production, and cyclooxygenase-2 (56,57).
Antidiarrheal activity In a study in mice, diarrhea was orally induced with 0.3 mL castor oil. The amount of wet and dry manure released by mice was counted every hour for 4 hours. In this experiment, the group of without K. galanga extract showed typical diarrhoea symptoms such as watery water and frequent bowel movements. K. galanga extract significantly inhibited the severity of diarrhoea in mice caused by castor oil (19).

Antineoplastic activity
The methanol extract of K. galanga has been notified to exhibit antineoplastic activity (58,59), which demonstrated inhibitory activity at the neoplasia stage as a factor in tumour emergence. When examined by Western blot and indirect immunofluorescent assay, it was proven that the methanol extract of K. galanga inhibited 12-O tetradecanoyl-phorbol-13-acetate that induced activation of the initial antigen of the Epstein-Barr virus in Raji cells (59). Anti-obesity activity The ethanol extract of K. galanga found to be beneficial to combat an obesity-induced dermatopathy system in Tsumura Suzuki obese diabetic (TSOD) mice as a model of obesity. It was shown a decrease in the body weight of rats and the thickness of the subcutaneous fat layer more than the polymethoxiflavonoid fraction, which was utilized as a dietary supplement in controlling skin disorders due to obesity (61).

Anti-mutagenicity activity
Anti-allergenic activity Polymethoxiflavone compounds relieved symptoms of type I allergy by suppressing cell degranulation of Basophilic Leukaemia (RBL2H3) (62).
Adaptogenic activity Chloroform, hexane, ethanol, and methanol extracts showed adaptogenic activity compared to the raw ginseng root powder (63). The dose of K. galanga extract (60% EtOH extract) increased the potential outlay of the whole body in humans (64). K. galanga is also known to improve health and physical health by reducing oxidative stress (65).

Analgesic activity
In a study, the in vivo analgesic activity of the alcoholic K. galanga extract was examined with the hot plate method and the tail-flick model in Wistar rats. The results indicated that the alcohol extract significantly augmented the stress tolerance capacity of animals at concentrations of 1200 and 600 mg/kg BW at 60 min via the hot plate method and 30 min via the tail-flick model (28).
Hypolipidemic activity A study showed that the oral administration of ethanol extract at a concentration of 20 mg/kg BW every day was effective in decreasing serum total cholesterol, phospholipids, triglycerides, and increasing serum high density lipoprotein levels in white Wistar rats fed high cholesterol diet for 4 weeks. Thus, the ethanol extract of K. galanga showed hypolipidemic activity but no active compound has been found to be responsible for this activity (66).

Hypopigmentary activity
In one study, the ethyl p-methoxycinnamate compound was isolated using nuclear magnetic resonance technique from chloroform fraction of K. galanga ethanol extract to evaluate activity in skin whitening on B16F10 murine melanoma cells. The results of this study indicated that ethyl p-methoxycinnamate significantly reduced melanin synthesis in B16F10-induced murine melanoma cells with α-melanocyte excite hormone. Thus, the ethyl p-methoxycinnamate compound from K. galanga might be expanded as a cosmetic in whitening skin (67).
Sedative activity Acetone extract from rhizome (200 mg/kg) and leaf (200 mg/kg) indicated a significant reduction in the onset and sleep duration of sodium thiopental induced rats, which certify its potential as sedative substance for central nervous system (19). Inhalation of hexane extract at doses ranging from 1.5 to 10 g/kg BW indicated an appreciable subtraction in locomotor activity in mice. This sedative activity is caused by ethyl-cinnamate and ethyl transp-methoxycinnamate compounds, which inhibit the locomotor activity of the central nervous system (37).

Amoebicidal activity
In a study evaluating the in vitro amoebicidal activity of non-polar and polar extracts using a microscope reported that non-polar extracts possessed amoebicidal property against Acanthamoeba castellanii, Acanthamoeba culbertsoni, and Acanthamoeba polyphaga. This study proves that K. galanga extract is effective in fighting intestinal parasites (68).

Vasorelaxant activity
Kaempferia galanga extract showed a dose-related decrease in basal mean arterial emphasis with maximum effect seen 5 to 10 minutes after injection (32). Ethyl cinnamate compound in a dose depending manner inhibited tonic contraction caused by increased entry of phenylephrine and potassium. However, this vasorelaxant activity was inversely proportional to aortic pre-treatment with indomethacin and methylene blue. This vasorelaxant mechanism might implicate retardation of calcium entry into vascular cells as well as the detachment of prostaglandins and nitric oxide from endothelial cells (69).
Wound healing activity The ethanol extract of K. galanga indicated wound healing activity in mice that was almost comparable to dexamethasone (70).

Toxicological study
Kaempferia galanga ethanol extract at concentrations of 50, 25, 100, and 800 mg/kg BW caused a reduction in motor activity, depression of the central nervous system, and decreased respiratory rate in mice. Administration of K. galanga ethanol extract to mice at the dose of up to 5 mg/kg BW did not result in death, nor was there any significant discrepancy in organ and body weight between the control group and the tested group. However, the ethanol extract of K. galanga 50, 25 and 100 mg/kg BW for 28 days resulted in a slight reduction in the number of lymphocytes in mice with all other parameters normal. The hexane fraction from K. galanga applied to rabbit skin did not show any signs of skin irritation (25).

Conclusion
To sum up, K. galanga is an important medicinal plant with many medicinal uses and has been widely used in various countries in the world because this plant has various pharmacological activities. In addition, further research on the use of K. galanga will increase the application of this plant in a wider and more suitable range.
Authors' contributions ARK, TIS, ANMA conceived of the presented idea; ARK, ANMA, GAP, and AF developed the article, wrote, and prepared the manuscript; NM encouraged; while TIS supervised the research and critical revision of the article. RHH, GAP, AF, and SCR made the final version. All authors read the manuscript and confirmed the publication of the final version.

Conflict of interests
There is no conflict of interest.

Ethical considerations
Ethical issues including text plagiarism, misconduct, manipulation or appropriation, data fabrication, falsification, redundant publication as well as duplicate submissions have been carefully observed by authors.

Funding/Support
This study funded by Universitas Airlangga, Surabaya, Indonesia.