Kaempferia galanga: A Multifaceted Medicinal Plant in Traditional and Modern Contexts

Introduction

The prevalence of chronic diseases associated with lifestyle choices is increasing at an alarming rate as the global population ages. Worldwide, human dietary habits represent the most crucial modifiable element in managing these chronic conditions. Studies show that maintaining traditional healthy eating practices and adopting a therapeutic plant-based diet can lower the risk of these diseases while boosting immunity (1). As a result, traditional medicinal botanical remedies, especially those used as food in traditional practices, are becoming more popular and in demand (2).

There are over 25,791 plant species recognized for their medicinal properties, of which 5,411 are included in the Red List of Threatened Species by the International Union for Conservation of Nature (IUCN) due to overexploitation (3). Many herbal remedies are being developed based on traditional knowledge. In anticipation of future pandemics, like the recent COVID-19 pandemic that started in early 2020, researchers have begun exploring the potential of developing new therapies from medicinal plants and their active compounds (4). It has been observed that adding botanical medicines with anti-inflammatory properties to anti-inflammatory diets can help reduce the worsening of COVID-19 symptoms associated with chronic conditions such as diabetes and obesity (5). Alongside widely known medicinal plant species, other botanical remedies traditionally used by local ethnic communities also hold significant importance in folk medicine. As global human mobility increases, urban populations are beginning to recognized these lesser-known species. The Zingiberaceae family is one such group, including many medicinal plants valued for their ethnomedicinal importance not only in India but also in various regions worldwide (6).

These plants have been employed in traditional medicine and are essential to cultural heritage. The most prevalent members of this family consist of Zingiber, Curcuma, Alpinia, and Kaempferia, among others (Figure 1) (7).

Phytochemistry

Major chemical constituents

Major chemical compounds found in K. galanga are phenolics, cyclic dipeptides, flavonoids, terpenoids, diarylheptanoids, essential oils and polysaccharides, which are mentioned below (Table 1).

Table 1. Chemical constituents of K. galanga.

S. No.	Chemical Constituents	Structure	CID
1	3 - carene		26049
2	Cadinene		441005
3	3H- 3a,7-methanoazulene		86185943
4	Heptadecane		12398
5	1,6-Cyclodecadiene		5365639
6	Camphene		6616
7	Limonene		22311
8	Alpha pinene		6654
9	Ethyl cinnamate		637758
10	Eucalyptol or 1,8-cineole		2758

Pharmacological activities

Toxicity studies and their potential adverse effects and contraindications

Toxicological investigations of K. galanga have already demonstrated a broad margin of safety. Some of the safety assessments that have already been done by some researchers are mentioned below: According to Kanjanapothi et al. (2004), an oral dose of 50,000 mg/kg of K. galanga rhizome ethanol extract was the highest amount that could be tolerated, and no deaths were recorded in rats. In both the male and female test groups, no variations were found in any of the parameters analyzed by hematological analysis. There is no skin irritation in pathology and histopathology. Also, no deaths were reported in 28-day subacute toxicity trials when 25, 50, or 100 mg/kg of the ethanolic K. galanga extract was given. Therefore, based on the above toxicological investigations, during the course of treatment, K. galanga is safe for the vital organs. They showed a broad margin of safety for essential organs. Potential adverse effects and contraindications were not observed at the tested doses; however, the lack of data in humans and on long-term use means caution is warranted, especially in pregnancy (16).

S. Siska et al. (2023) investigated the acute toxicity of the ethyl acetate fraction of KG (EAFKG) using measures such as liver and kidney histological morphology and blood chemistry values. In this investigation, 40 DDY strain mice weighing between 20 and 35 g were employed, including both male and female mice. For each sex, there were four groups of mice. Groups 1, 2, 3, and 4 received the EAFKG orally at dosages of 0.128, 0.64, 3.2, and 16 g/kg BW, respectively. Observations were made during the entire day. Using a clinical spectrophotometer, serum levels of AST, ALT, and creatinine were assessed. The test results showed that there were no fatalities in either the male or female mouse groups. EAFKG's rhizome is practically non-toxic (LD50 > 15 g/kg BW). There was no recorded mortality. A blood test did not reveal any notable alterations in the kidney or liver. The drug is acutely safe, and practically no acute organ toxicity is seen even at very high doses (17).

Shawkat et al. (2015) investigated the sedative potential of different rhizome and leaf extracts of K. galanga in Swiss albino mice. Oral administration of acetone, petroleum ether, chloroform, and methanol extracts at 100 and 200 mg/kg showed no toxicity or mortality. This indicates good tolerability. In locomotion parameter assessment, the acetone leaf extract (200 mg/kg) caused up to 95% suppression, which is higher than that of diazepam (70%). The finding suggests that K. galanga is safe enough to be used, but it exhibits potent sedative and CNS depressant properties due to its traditional use for restlessness, stress and anxiety. No mortality or overt toxicity is observed at doses of 100–200 mg/kg, but a risk of sedation and CNS depression is observed if combined with alcohol, benzodiazepines or barbiturates (18). Despite K. galanga's long history of use as TCHM, its comprehensive toxicity and safety assessments are still unknown, according to Amuamuta et al (2017). The acute and subacute toxicity tests of the ethanol extract from its rhizomes indicate that it exhibits no noticeable toxicity concerning morbidity or mortality, with a maximum single oral dose of up to 5,000 mg/kg (body weight) and a daily dose of 1,000 mg/kg (body weight) administered for a consecutive period of 30 days. No such contraindication is observed in animals, but extrapolation to humans still requires caution, even though systemic safety is observed even with prolonged administration (19).

In an in vitro investigation, Jacob et al. (2023) found that many bioactive compounds found in K. galanga's rhizome support the plant's anti-inflammatory, anticancer, antibacterial, and antioxidant qualities. Therefore, additional in vivo research could shed light on whether K. galanga rhizome extracts can be employed alongside existing conventional treatments for chronic illnesses. An in vitro toxicity evaluation of K. galanga rhizome extract showed dose-dependent cytotoxicity against HeLa cancer cells. The extract had an IC50 value of 25.04 µg/mL and induced apoptosis in 24.63% of cells. Both analyses show that the extract exhibits selective therapeutic value of anticancer activity rather than general toxicity. At higher concentrations, the extracts show cytotoxic effects even on non-cancerous cells, leading to cell death, which requires in vivo validation (20).

Umar et al. (2012) investigated the finding that K. galanga has anti-inflammatory activity. They isolated K. galanga extract using petroleum ether, chloroform, and methanol. Extract of the plant (2 g/kg per animal) was tested for its potency in addressing inflammation through the carrageenan-induced paw oedema model. The chloroform extract demonstrated the highest level of inhibition (42.9%) in comparison to the control (p < 0.001). Consequently, it underwent further fractionation through repeated washing with chloroform, hexane, and a hexane-chloroform mixture (1:1). The chloroform fraction (1 g/kg) exhibited the most significant inhibitory effect (51.9%, p < 0.001) on carrageenan-induced oedema. This chloroform fraction was subsequently separated using a mixture of chloroform and hexane-chloroform (1:3). The chloroform fraction (1 g/kg) exhibited the most significant inhibitory effect (51.9%, p < 0.001) on carrageenan-induced oedema. This chloroform fraction was subsequently separated using a combination of chloroform and hexane-chloroform (1:3). The main component of the active sub-fraction, ethyl-p-methoxycinnamate (EPMC), was identified through GC-MS analysis and subsequently recrystallized. Carrageenan-induced oedema was dose-dependently reduced by EPMC, with an effective dose (ED50) of 100 mg/kg. At higher concentrations, EPMC modulates immune function, which particularly exacerbates immune suppression to show an anti-inflammatory response, thereby increasing susceptibility to infections. This is why this drug is contraindicated in patients taking immunosuppressants or those with chronic immune-related conditions (21).

Adulteration and identification

Application in food and industry

A variety of medicinal and culinary uses of K. galanga for health benefits, food, and nutritional purposes are well documented (22). Aromatic ginger is used as a therapeutic spice in Indian, Chinese, and Southeast Asian cuisines. A huge portion of the population consumes it in health-promoting pickles. Scientific studies on its specific nutritional and safety status, as well as its practical use, have not yet been conducted. Creating novel health products based on "whole foods" or specific plant bioactivity has been a hot area of study. Made from K. galanga tubers, "Beras Kencur" is a well-known Java beverage. The essential oil that is derived from the rhizome and leaves is used in Bangladesh to flavor food and drinks and to fragrance vinegar (23). In Indonesia and Malaysia, traditional herbal preparations known as 'Makjun' and 'Jamu' are eaten for health benefits.

Biotechnological advancement

Conclusion

Reviewers and numerous researchers have claimed that the plant possesses a wide range of pharmacological actions. The active components of K. galanga rhizome extract have been shown to suppress gastric, colon, oral and multiple myeloma cancer cells through mechanisms that involve apoptosis, cytotoxicity, and the suppression of tumour cell growth. It may impact the course of the cell cycle of HepG2 cells and trigger death. Regarding anti-obesity initiatives, in a study, Tsumura Suzuki Obese Diabetes (TSOD) mice were given 1 to 3 per cent extracts of K. galanga for eight weeks. All problems, including body weight growth, peripheral neuropathy, glucose intolerance, hyperinsulinemia, visceral fat buildup, insulin resistance, and abnormal lipid metabolism, were inhibited in the treated mice. Escherichia coli, Staphylococcus aureus, Pseudomonas, Aspergillus, and Candida albicans are all susceptible to the antibacterial properties of K. galanga rhizome extract. Several pathogenic bacteria and fungi were suppressed in a disc diffusion study utilising a disc impregnated with 10 μL with ethanolic and methanolic extracts of K. galanga, with the highest inhibition zone (21.3 ± 0.08) against Staphylococcus aureus.

Anti-inflammatory activity: iNOS mRNA expression was significantly reduced by the chemical and plant extract, whereas COX-2 mRNA expression was not. In vivo experiments revealed that the most efficient fractions for lowering rat paw oedema were hexane and chloroform. Because it has generated favorable results, including increasing skin moisturization, reducing wrinkles, and improving skin, it can also be used for external applications in the cosmetics and pharmaceutical industries. As a natural acne remedy, the Kaempferia plant extract decreased the buildup of fat and triglycerides in sebocytes, hence lowering skin infections. Based on all of the pharmacological activities, it has been determined that the plant has promise for treating a variety of diseases in terms of formulation. Thus, from all the reported information available, the plant has various potential anticancer, anti-inflammatory, antibacterial, antifungal, and antimicrobial properties, which help in the treatment of diseases. Keeping all this in mind, the reviewers and researchers may explore these properties in the formulation and development of a suitable formulation for their clinical importance in the near future.