Anti-Inflammatory Activity of Alpinia malaccensis (Burm. f.) Roscoe and Kaempferia galanga L. Rhizome Essential Oil Gel Formulations by Carrageenan Induction Method

Sains Malaysiana 51(5)(2022): 1411-1424http://doi.org/10.17576/jsm-2022-5105-12 

ABSTRACT Bioactive compound from essential oils of Alpinia malaccensis(AM) and Kaempferia galanga (KG) rhizomes, respectively, such as methyl cinnamate and ethyl-p-methoxycinnamate (EPMS) have been reported to have anti-inflammatory activity. The present study aimed to determine the topical anti-inflammatory activity of 3 gel formulations (Formula 1, 2 and 3) having different concentrations of essential oil from AM and KG rhizomes. The gelling agent used in this study was Carbopol 934. The physicochemical parameters of the gel formulations such as organoleptic, pH, viscosity, and spreadability as well as hedonic test were also examined. The anti-inflammatory activity assay was carried out using the carrageenan induced rat paws edema method. The chemical composition of AM and KG rhizomes was identified by GC-MS with LRI index. The major essential oils content in AM and KG rhizome was methyl cinnamate (58.80%) and ethyl-p-methoxy cinnamate (59.68%), respectively. Based on the results of physical evaluation, hedonic test and anti-inflammatory activity, Formula 1 with 5% AM and 2.5% KG essential oils is the best formula with % inflammation inhibition of 36.32 ± 6.32%.

INTRODUCTION Inflammation is part of the body’s immune response towards tissue injuries caused by physical trauma, chemical substances, or microbial infection (Chen et al. 2017). Such response is via deactivation of invading organisms in the tissues, elimination of irritants and regulation of tissue repair (Woodell-May & Sommerfeld 2020). The most common inflammation treatment is the NSAIDs (Non-Steroid Anti-Inflammatory) drugs (Barkin 2015). However, NSAIDs cause side effects such as gastric mucosal damage (Matsui et al. 2011). To overcome this shortcoming, the topical formulation was a great alternative that could minimize gastric side effects. However, this strategy still has disadvantages because topical NSAID exhibits poor bioavailability and it could lead to drug accumulation in the area of inflammation even after remission (Rannou et al. 2016). Therefore, the discovery of new potent anti-inflammatory active compounds with fewer side effects is important in anti-inflammatory drug discovery. The rhizomes of Alpinia malaccensis [Burm. F.] (AM) has been reported to have antipyretic, analgesic, and anti-inflammatory effects (Sethi et al. 2017). Besides AM, Kaempferia galanga L. (KG) has also been reported to have antiinflammatory effects (Jagadish et al. 2016; Sulaiman et al. 2008; Umar et al. 2012). 

Methyl cinnamate and ethyl-p-methoxycinnamate in the rhizomes of AM and KG, respectively, have anti-inflammatory activity (Gui et al. 2018). Ethylp-methoxycinnamate of KG inhibits inflammation by suppressing interleukin-1β, tumor necrosis factor-α, and angiogenesis hence blocking the endothelial functions (Umar et al. 2014). While, methyl cinnamate inhibits the cytokine interleukin-1β that plays role as a mediator of the inflammatory response (Lima et al. 2013; Lopez-Castejon & Brough 2011). Since both ethyl-p-methoxycinnamate and methyl cinnamate inhibit interleukin-1β, the combination of both in one preparation could exhibit potent anti-inflammatory activity. The combination of both essential oils; ethyl-pmethoxycinnamate and methyl cinnamate for topical dosage as an anti-inflammatory agent has yet been reported. Study on the combined effect of both essential oils is necessary to produce topical gel products containing essential oils as aromatherapy that can be absorbed through the skin and olfactory system (Muchtaridi et al. 2011). In previous studies, physical evaluations have been performed including organoleptic, homogeneity, pH, viscosity, and dispersibility of 6 formulas based on variations in a gel base for 28 days of storage. The gel base used included Hydroxypropyl Methyl Cellulose (HPMC) with concentration of 4, 6, and 8% and Carbopol 934 with a concentration of 0.5, 0.75, and 1%. From this evaluation, the best gel base formulation based on the optimization results was carbopol 934. Further physical evaluation was performed using gel base carbopol 934 at a concentration of 0.5, 0.75, and 1% in combination with 1% AM and 0.5% KG essential oil and the best formula selected for anti-inflammatory activity was 0.75% Carbopol gel base (Fitriani 2018). The anti-inflammatory activity was performed by preparing the gel containing AM and KG essential oils into 3 dosages using the carrageenan induction method on male white rats (wistar strain). Sethi et al. (2017) reported that oral dose of AM rhizome extract reduced inflammation up to 32.69% at a dose of 100 mg/kgBW with the carrageenan induction method. The oral dose using KG rhizome extract also shows a reduction of inflammation at a dose of 18 mg/kgBW with 42.24 ± 6.19% reduction; 36 mg/kgBW, 40.08 ± 4.65% reduction and 45 mg/kgBW with 32.62 ± 3.1% reduction (Hasanah et al. 2011). According to Soeratri et al. (2014), the topical anti-inflammatory dose of KG essential oil was determined by comparing the antiinflammatory activity of 1% Na-Diclofenac solution with 5.59% ethyl-p-methoxycinnamic acid (EPMS). Ethyl-pmethoxycinnamic (EPMS) is the main ingredient in KG’s essential oil, thus the effective dose for KG’s essential oil in gel preparations is 5% (Soeratri et al. 2014). In this study, an anti-inflammatory topical dosage form was prepared to determine a systemic effect that is absorbed into the blood vessels of the skin. This is similar to the oral administration of anti-inflammatory drugs that are absorbed through the intestinal mucosa (Hua 2020).

The composition of AM rhizome essential oils was determined by comparing the oral dose of 100 and 45 mg/kgBW with ratio 2:1 for the oral dose of AM:KG. Therefore, the topical dose of KG and AM’s essential oil is 5 and 10%, respectively. Furthermore, a gel formulation with 3 variations of dosage for the essential oil of AM:KG was prepared based on a ratio of 2 :1 consisting of Formula I (concentration of essential oil of AM 5% and KG 2.5%); Formula II (concentration of essential oils of AM 10% and KG 5%) and dose III (concentration of essential oils of AM 20% and KG 10 %).

Sains Malaysiana 51(5)(2022): 1411-1424http://doi.org/10.17576/jsm-2022-5105-12