Effect of Kencur (Kaempferia galanga L.) Ethanolic Extract Treatment on Cerebral Caspase-3 Expression in Traumatic Brain Injury Rat Models.

Background: Traumatic brain injury is one of the most common forms of trauma and causes significant morbidity and mortality. Kencur (Kaempferia galanga L.) ethanolic extract is known to contain substances that could theoretically inhibit unfavourable cellular processes, including oxidative stress and inflammation. This research aimed to study Kencur's anti-apoptosis activity through the inhibition of caspase-3. Methods: This is a true experimental post-test-only group design study, using male Wistar rats (Ratus novergicus) with weight-drop-induced traumatic brain injury. The subjects in this study were divided into four groups: two Control groups (Groups A and B) and two Therapy groups (Groups C and D). Groups C and D differed in the dose of Kencur ethanolic extract administered (600 mg/kgBW/day and 1,200 mg/kgBW/day, respectively). The Therapy groups were then subdivided into those receiving therapy for 24 h (C-24 and D-24) and those receiving therapy for 48 h (C-48 and D-48). Caspase-3 expression in brain tissue was evaluated at the end of the therapy using immunohistochemistry. All groups were subjected to a Kruskal-Wallis comparison test and the investigation continued with a Mann-Whitney U test to compare the two groups. Results: In traumatic brain injury rat models treated with Kaempferia galanga L. ethanolic extract at doses of 1,200 mg/kgBW/day within 48 h of therapy (D-48) compared to those who were not treated, there was a significant change in the cerebral expression of caspase-3 (P = 0.016). There was also a significant difference between the two doses of intervention (C-24 at 600 mg/kgBW/day and D-48 at 1,200 mg/kgBW/day; P = 0.016). Conclusion: With a minimum of 48 h of treatment split into two doses, Kencur (Kaempferia galanga L.) ethanolic extract can decrease caspase-3 expression in rats with traumatic brain injury.

Protective effects of an alcoholic extract of Kaempferia galanga L. rhizome on ethanol-induced gastric ulcer in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: The rhizome of Kaempferia galanga L., a medicinal and edible Plant, was widely distributed in many Asian and African counties. It has been traditionally used to treat gastroenteritis, hypertension, rheumatism and asthma. However, there is a lack of modern pharmacology studies regarding its anti-gastric ulcer activity. AIM OF THE STUDY: The objective of this study is to investigate the protective effects of an extract from K. galanga L. rhizome (Kge) and its active components kaempferol and luteolin on ethanol-induced gastric ulcer. MATERIALS AND METHODS: The kge was prepared by ultrasonic-assisted extraction, and the contents of kaempferol and luteolin were determined by HPLC. The mice were randomly divided into seven groups: blank control (0.5 % CMC-Na; 0.1 mL/10 g), untreatment (0.5 % CMC-Na; 0.1 mL/10 g), Kge (100, 200 and 400 mg/kg), kaempferol (100 mg/kg) and luteolin (100 mg/kg) groups. The mice were treated intragastrically once daily for 7 days. At 1 h post the last administration, the mice in all groups except the blank control group were intragastrically administrated with anhydrous alcohol (0.1 mL/10 g) once to induce gastric ulcer. Then, fasting was continued for 1 h, followed by sample collection for evaluation by enzyme-linked immunosorbent assay and real-time reverse transcription polymerase chain reaction assay. RESULTS: The contents of kaempferol and luteolin in Kge were determined as 3713 µg/g and 2510 µg/g, respectively. Alcohol induced severely damages with edema, inflammatory cell infiltration and bleeding, and the ulcer index was 17.63 %. After pre-treatment with Kge (100, 200 and 400 mg/kg), kaempferol and luteolin, the pathological lesions were obviously alleviated and ulcer indices were reduced to 13.42 %, 11.65 %, 6.54 %, 3.58 % and 3.85 %, respectively. In untreated group, the contents of Ca2+, myeloperoxidase, malondialdehyde, NO, cyclic adenosine monophosphate and histamine were significantly increased, while the contents of hexosamine, superoxide dismutase, glutathione peroxidase, and prostaglandin E2 were significantly decreased; the transcriptional levels of IL-1α, IL-1ß, IL-6, calcitonin gene related peptide, substance P, M3 muscarinic acetylcholine receptor, histamine H2 receptor, cholecystokinin 2 receptor and H+/K+ ATPase were significantly increased when compared with the blank control group. After pre-treatment, all of these changes were alleviated, even returned to normal levels. Kge exhibited anti-gastric ulcer activity and the high dose of Kge (400 mg/kg) exhibited comparable activity to that of kaempferol and luteolin. CONCLUSION: The study showed that K. galanga L., kaempferol, and luteolin have protective effects against ethanol-induced gastric ulcers. This is achieved by regulating the mucosal barrier, oxidative stress, and gastric regulatory mediators, as well as inhibiting the TRPV1 signaling pathway and gastric acid secretion, ultimately reducing the gastric ulcer index.

Six new phenylpropanoids from Kaempferia galanga L. and their anti-inflammatory activity.

Kaempferia galanga L. is an aromatic medicinal plant belonging to the Zingiberaceae family. Its rhizome has been widely used as traditional Chinese medicine and a flavor spice for a long time. In this study, six previously undescribed phenylpropanoids, including four [2+2]-cycloaddition-derived cyclobutane natural products (1-4), and two phenylpropanoids (5-6) were isolated from the rhizomes of K. galanga L. Their structures were elucidated by spectroscopic methods, single-crystal X-ray diffraction, NMR calculation, and ECD spectra calculation. These cyclobutane derivatives were isolated from K. galanga for the first time. Furthermore, compounds 1-6 were evaluated for the potential inhibitory activities on NO production and NF-κB nuclear translocation in LPS-triggered RAW 264.7 macrophages. The results showed that the isolated compounds have a moderate anti-inflammatory activity measured on their potency to inhibit NO production and the expression of iNOS and COX-2. Additionally, compound 2 effectively suppressed NF-κB nuclear translocation at a concentration of 40 µM.

In-silico molecular docking and molecular dynamic simulation of γ-elemene and caryophyllene identified from the essential oil of Kaempferia galanga L. against biofilm forming proteins, CrtM and SarA of Staphylococcus aureus.

Medicinal plants play an important role as antimicrobials by inhibiting various key targets of diverse microorganisms. A major antimicrobial component of plants is its essential oil, which are increasingly being studied for their antimicrobial properties as well as for their potential role in the inhibition of biofilm formation. In the present study, essential oil from Kaempferia galanga L was isolated resulting in the identification of eleven compounds. Of these, two of the compounds, γ-elemene and caryophyllene were found to dock with the target proteins, CrtM and SarA of Staphylococcus aureus, which are essential for the formation of biofilm. γ-elemene demonstrated the best binding affinity with CrtM with binding energy of -8.1 kcal/mol whereas caryophyllene and its derivative isocaryophyllene showed the best binding with SarA with binding energy -6.1 kcal/mol. ADMET study of the compounds also revealed that the compounds are non-toxic and can be used as probable compounds for inhibition of biofilms. Molecular dynamic simulation studies revealed high affinity of binding and stability of the molecules with their targets. PCA analysis helped in identifying the principal motions occurring within a trajectory that are essential in inducing conformational changes.Communicated by Ramaswamy H. Sarma.

Chemical composition of the Kaempferia galanga L. essential oil and its in vitro and in vivo antioxidant activities.

Introduction: Oxidative stress is closely related to the development of many diseases. Essential oils (EOs) show potent antioxidant activity from natural sources. Kaempferia galanga L. is an important medicine rich in high-value essential oil (KGEO). However, the antioxidant activity of KGEO remains to be fully studied. Methods: Chemical composition of KGEO was analyzed using gas chromatography-mass spectrometry (GC-MS). The antioxidant activity was determined using the DPPH, ABTS, hydroxyl radical scavenging assays and reducing power assay in vitro. A zebrafish model was used to evaluate the protective effect of KGEO against H2O2-induced oxidative stress damage in vivo. Results: The major components of KGEO were found to be trans ethyl p-methoxycinnamate (32.01%), n-pentadecane (29.14%) and trans ethyl cinnamate (19.50%). In vitro pharmacological results showed that KGEO had good free radical scavenging capacity in DPPH, ABTS, and hydroxyl radical scavenging assays (IC50 values: 19.77 ± 1.28, 1.41 ± 0.01, and 3.09 ± 0.34 mg/mL, respectively) and weak reducing capacity in the reducing power assay (EC50 value: 389.38 ± 4.07 mg/mL). In vivo zebrafish experiments results indicated that the survival rate and heart rate increased, and ROS generation, cell death, and lipid peroxidation were attenuated after KGEO treatment. In addition, a decrease in malondialdehyde (MDA) levels and increases in superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) activities were observed in the KGEO-treated groups. Discussion: This study validated the in vitro and in vivo antioxidant activities of KGEO, which provides a theoretical basis for a profound study of KGEO and its application in the pharmaceutical, food and cosmetic industries.

Kaempferia galanga L. extract and its main component, ethyl p-methoxycinnamate, inhibit the proliferation of Ehrlich ascites tumor cells by suppressing TFAM expression.

Kaempferia galanga L. shows anti-cancer effects; however, the underling mechanism remains unclear. In this study, we explored the underlying mechanism of the anti-cancer effects of Kaempferia galanga L. Kaempferia galanga L. rhizome extracts (KGEs) suppressed Ehrlich ascites tumor cell (EATC) proliferation by inhibiting S-phase progression. The main component of KGE is ethyl p-methoxycinnamate (EMC), which exhibits the same anti-proliferative effect as KGE. Furthermore, EMC induced the downregulation of cyclin D1 and upregulation of p21. EMC also decreased the expression of mitochondrial transcription factor A (TFAM) but did not significantly change mitochondrial DNA copy number and membrane potential. Phosphorylation at Ser62 of c-Myc, a transcription factor of TFAM, was decreased by EMC treatment, which might be due to the suppression of H-ras expression. These results indicate that EMC is the active compound responsible for the anti-cancer effect of KGE and suppresses EATC proliferation by regulating the protein expression of cyclin D1 and p21; TFAM may also regulate the expression of these genes. In addition, we investigated the anticancer effects of KGE and EMC in vivo using EATC bearing mice. The volume of ascites fluid was significantly increased by intraperitoneal administration of EATC. However, the increase in the volume of ascites fluid was suppressed by oral administration of EMC and KGE. This study provides novel insights into the association between the anti-cancer effects of natural compounds and TFAM, indicating that TFAM might be a potential therapeutic target.

Antiviral effect of an extract from Kaempferia galanga L. rhizome in mice infected with pseudorabies virus.

Pseudorabies virus (PrV) is one of the most important herpesviruses which can cause severe diseases in many mammals and some avian species. In recent years, repeated outbreaks of pseudorabies worldwide indicated an urgent need for new control measures. The results described in this study demonstrated that an extract prepared from the rhizome of Kaempferia galanga L (Kge), which consisted of flavonoids (2.82%), saccharides (61.37%), phenols (1.22%) and saponins (3.10%), possessed a potent anti-PrV activity. In PK-15 cells, Kge treatment inhibited PrV-induced cell death by more than 90% at a dose of 200 µg/mL. The 50% inhibitory concentration (IC50) was 55.85 µg/mL. In the PrV-infected mice treated with Kge, the survival rate was up to 60% at day 6 post-infection, while the infected mice without Kge treatment all died. The virus titers in the brains of the Kge-treated infected mice were significantly reduced. Kge treatment also alleviated the severity of the PrV-induced lesions in the heart, liver, spleen, lung and kidney. Kge exhibited immune-regulating activity through the regulation of cytokines (IFN-α, IFN-ß, IL-4, IL-6 and TNF-α) in the serum of PrV-infected mice, suggesting that one possible mechanism of anti-PrV activity was through the regulation of immune function. These results suggested that Kge could be a promising drug candidate for treating PrV infections.

Anti-Inflammatory Activity and Wound Healing Effect of Kaempferia galanga L. Rhizome on the Chemical-Induced Oral Mucosal Ulcer in Wistar Rats.

Introduction: Kaempferia galanga L. (K. galanga; local name kencur, Zingiberaceae) is a plant commonly used as a kitchen spice, and empirically it is often used for medicinal purposes. This plant has been shown to have an anti-inflammatory role, but no research has been found on its effect on oral mucosal ulcer. This study aimed to investigate anti-inflammatory activity and wound healing effect of the ethanol extract of K. galanga L. rhizome (EEKG) on the chemical-induced oral mucosal ulcer in Wistar rats. Methods: In this study, 35 rats were divided into 7 groups (normal, negative, triamcinolone acetonide, and 4 EEKG groups). Acetic acid 70% was used as the oral mucosal ulcer inducer. Parameters observed were macroscopic and microscopic histopathological examinations. Results: The results revealed that dose of 0.5% of the EEKG was effective in increasing the percent recovery of ulcer area and inflammation sign scores. Meanwhile, doses of 0.5-2% of EEKG were effective in reducing the histopathological score. Interestingly, topical EEKG in our study was more effective compared with triamcinolone acetonide (the conventional therapy for oral mucosal ulceration). Discussion: The EEKG has been confirmed its anti-inflammatory activity by accelerating the healing process on the chemical-induced oral mucosal ulcer in Wistar rats, based on the percent recovery of the ulcer area, the percent recovery of the inflammation sign score, and the histopathology score. Conclusion: Taken together, K. galanga L. is very potential to be developed as a prospective phytopharmaceutical for the treatment of oral mucosal ulceration in human after clinical trials.

Insecticidal and Feeding Deterrent Effects of Kaempferia galanga L. and Amomum subulatum on Pieris rapae L. Larva.

<b>Background and Objective:</b> <i>Pieris rapae</i> L., is one of the most widespread and destructive pests of cruciferous plants. At present, synthetic chemical insecticide is still the main approach to control this pest despite several disadvantages to human health and the wildlife environment as well as biological resistance. To search for plants having insecticidal activity, the biological effects of two medicinal plants <i>Kaempferia galanga</i> L. and <i>Amomum subulatum </i>on <i>Pieris rapae</i> L., were investigated. <b>Materials and Methods:</b> The methanol extracts of dry rhizomes and fruits of <i>Kaempferia galanga</i> L. and <i>Amomum subulatum </i>were used to determine the mortality, feeding and oviposition deterrence of larvae and adult of <i>Pieris rapae</i> L. <b>Results:</b> <i>Kaempferia galanga</i> L. and <i>Amomum subulatum</i> exhibited insecticidal activity against <i>Pieris rapae</i> L., with LC₅₀ values of 2.11 and 11.80% (w/v), respectively. In the antifeedant test, <i>Kaempferia galanga</i> L., extract showed no significant difference with the control at the low concentration (0.5 and 1%). Whereas, with a concentration of 0.5%, <i>Amomum subulatum</i> extract demonstrated a high antifeedant effect on <i>Pieris rapae</i> L., larvae. In addition, plants treated with these two extracts reduced eggs laid by <i>Pieris rapae</i> L., in field conditions showing the oviposition deterrent properties. <b>Conclusion:</b> These results indicated that <i>Kaempferia galanga</i> L. and <i>Amomum subulatum </i>extracts have insecticidal substances against <i>Pieris rapae </i>L., which can be used for developing effective pesticides or/and oviposition deterrents for integrated pest management.

Kaempferia galanga L.: Progresses in Phytochemistry, Pharmacology, Toxicology and Ethnomedicinal Uses.

K. galanga is an aromatic medicinal herb. It is locally to India and distributed in China, Myanmar, Indonesia, Malaysia, and Thailand. K. galanga is a Traditional Chinese Herb Medicine (TCHM), which has been applied to treat cold, dry cough, toothaches, rheumatism, hypertension and so on. In addition, it has been used widely as spices since its highly aromas. The aim of this review is to compile and update the current progresses of ethnomedicinal uses, phytochemistry, pharmacology and toxicology of K. galanga. All the data on K. galanga were based on different classical literary works, multiple electronic databases including SciFinder, Web of Science, PubMed, etc. The results showed that ninety-seven compounds have been identified from rhizome of K. galanga, including terpenoids, phenolics, cyclic dipeptides, flavonoids, diarylheptanoids, fatty acids and esters. Modern pharmacology studies revealed that extracts or secondary metabolites of the herb possessed anti-inflammatory, anti-oxidant, anti-tumorous, anti-bacterial, and anti-angiogenesis effects, which were closely related to its abundant ethnomedicinal uses. In conclusion, although previous research works have provided various information of K. galanga, more in-depth studies are still necessary to systemically evaluate phytochemistry, pharmacological activities, toxicity and quality control of this herb.

Phytochemistry, pharmacological activities and uses of traditional medicinal plant Kaempferia galanga L. - An overview.

ETHNOPHARMACOLOGICAL RELEVANCE: Kaempferia galanga L. is a stemless, rhizomatous, aromatic, perennial and indigenous herb. It is native to India and distributed in China, Bangladesh, Myanmar, Sri Lanka, Japan, Thailand, Indonesia, Malaysia, Vietnam, Laos, Sudan, Nigeria and South Africa. It is an important Indian medicinal herb that has a long history of use in the treatment of several kinds of human ailments including vata ailments like cough and cold, fever, headache, pains disorders, skin diseases, rheumatic diseases, arthritis, joint fractures, vertigo, wounds, gastritis, antidote for snake venoms, inflammation, blood vomiting, mouth sores and tongue blisters in infants. Moreover, the rhizomes of this plant are highly aromatic and have been used widely as spices, in food flavoring, pickles, cosmetics and in perfumery products. AIM OF THE REVIEW: This paper aimed to provide a critical review of current scenario on K. galanga. This review provides a current data on diversity, phytochemistry, pharmacological activities and traditional uses of K. galanga. MATERIALS AND METHODS: The information and data on K. galanga were collated from various resources like ethnobotanical textbooks and literature databases such as PubMed, Science Direct, Wiley, Springer, Tailor and Francis, Scopus, Inflibnet, Google and Google Scholar. RESULTS: The forty-nine phytochemicals including esters, terpenoids, flavonoids, thiourea derivatives, polysaccharides, diarylheptanoids, phenolic acids, phenolic glycoside and cyclic lipodepsipeptide have been hitherto isolated and characterized. The major bioactive compounds extracted from the rhizome of K. galanga were ethyl p-methoxycinnamate, ethyl cinnamate, kaempferol, kaempferide, kaempsulfonic acids, kaemgalangol A, xylose, cystargamide B and 3-caren-5-one. Various studies demonstrated that the K. galanga and its constituents possess several pharmacological activities like antimicrobial, antioxidant, amebicidal, analgesic, anti-inflammatory, anti-tuberculosis, anti-dengue, anti-nociceptive, anti-angiogenic, anticancer, hyperlipidemic, hypopigmentary, osteolysis, larvicidal, insecticidal and mosquito repellent, nematocidal, sedative, sniffing, vasorelaxant and wound healing. CONCLUSION: Kaempferia galanga L. is a valuable medicinal plant which is used traditionally in India to treat a wide variety of ailments. A number of bioactive phytochemicals like esters, terpenoids, flavonoids, polysaccharides, diarylheptanoids, cyclic lipodepsipeptide, phenolic acids and glucoside have been isolated from the rhizomes of K. galanga by several researchers. These phytochemicals are highly bioactive and exhibit various pharmacological activities.

Extraction, characterization and evaluation of Kaempferia galanga L. (Zingiberaceae) rhizome extracts against acute and chronic inflammation in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: The rhizomes of an acaulescent perennial herb, Kaempferia galanga Linn (Family: Zingiberaceae), used as traditional ayurvedic herb to get relief from indigestion, swelling, pain, high blood pressure and dyslipidemia. AIM OF THE STUDY: To prepare and characterize various extracts of Kaempferia galanga (K. galanga) for their comparative evaluation for the identification of the most efficacious extract and its possible pharmacological implication in acute and chronic inflammatory paradigm. MATERIALS AND METHODS: Dried and powdered rhizome of K. galanga was subjected to alcoholic extraction as well as successive extractions with various solvents. After phytochemical characterization, all the extracts were standardized for the presence of ethyl-p-methoxycinnamate. The extracts, and the isolated compound, were tested against carrageenan-induced acute inflammation in rats. The most promising extract was tested against adjuvant-induced chronic inflammation in rats. Further, local myeloperoxidase (MPO) levels were investigated to establish the possible mechanism of action. RESULTS: Among the extracts, petroleum ether extract (SKG-1) and crude alcoholic extract (KG) had the maximum quantity of ethyl-p-methoxycinnamate. SKG-1 (300mg/kg) was found effective against acute inflammation in rats. Further, SKG-1 (100mg/kg) reversed the inflammation and elevated MPO levels found in the chronic model. CONCLUSIONS: The results suggest that among all the extracts of K. galanga, SKG-1 effectively suppresses the progression of acute and chronic inflammation in rats by inhibition of neutrophil infiltration.