Kaempferia parviflora Wall. ex Baker

Synonyms

Kaempferia rubromarginata (S.Q.Tong) R.J.Searle, Stahlianthus rubromarginatus S.Q.Tong [1]

Vernacular Names

English Black ginger, black galingale, black ginseng [2]
India Kalahood [4]
Thailand Krachai dam [2]
Myanmar Gamin-ni [46]
Bangladesh Kalahood [4]
Germany Ingwer, schwarze galgantwurzel, schwarzer ginseng, Siamesischer ginseng [2].

General Information

Description

Kaempferia parviflora is a member of the Zingiberaceae family. It is a stemless rhizomatous herb that can reach up to 20 cm, tall. The rhizomes are small and of deep purple colour. The leaves are 8-16 cm long, thin, rounded at the base, plain green. The petiole is short and channeled. The flowers are few in a sessile central tuft. The bracts are 2.5 cm, lanceolate and green. The calyx is longer than the bract. The corolla-tube in 3 cm; segments are greenish, 1 cm long, upper ascending and rather concave. The lip is 0.75-1.0 cm, subemarginate with the anther-crest obtuse and broad as the long. [3]

Plant Part Used

Rhizome

Chemical Constituents

K. parviflora has been reported to contain 1α,3α,4β-trihydroxy-9-cadinen-8-one, 4α-acetoxycadina-2,9-diene-1,8-dione; 5,7-dimethoxyflavone, 5,7,4'-trimethoxyflavone, 5,7,3',4'-tetramethoxyflavone, 3,5,7,4'-tetramethoxyflavone, 3,5,7,3',4'-pentamethoxyflavone, 5-hydroxy-7-methoxyflavone, 5-hydroxy-3,7-dimethoxyflavone, rel-(5aS,10bS)-5a,10b-dihydro-1,3,5a,9-tetrahydroxy-8-methoxy-6H-benz[b]indeno[1,2-d]furan-6-one 5a-O-[α-L-rhamnopyranosyl-(1-->6)-β-d-glucopyranoside], rel-5aS,10bR isomer;  (2R,3S,4S)-3-O-[α-L-rhamnopyranosyl-(1-->6)-β-d-glucopyranosyl]-3'-O-methyl-ent-epicatechin-(2α-->O-->3,4α-->4)-(5aS,10bS)-5a,10b-dihydro-1,3,5a,9-tetrahydroxy-8-methoxy-6H-benz[b]indeno[1,2-d]furan-6-one 5a-O-[α-L-rhamnopyranosyl-(1-->6)-β-D-glucopyranoside], flav-3-en-3-ol glycosides, and kaempferiaosides A-F. [5][6][7][8][9][10][11][15]

Traditional Uses

K. parviflora is essentially a Thai medicinal plant and knowledge of its uses in other places including Malaysia has not been recorded. In Thailand the rhizome had been promoted for health and treatment of digestive disorders and gastric ulcer [12]. The rhizome also has been used in the treatment of gout, aphthous ulcer, peptic ulcer and abscesses [13].

Preclinical Data

Pharmacology

Antimicrobial activity

Antiplasmodial activity

Two flavonoids (5,7,4’-trimethoxyflavone and 5,7,3’,4’-tetramethoxyflavone) from K. parviflora rhizome exhibited antiplasmodial activity against Plasmodium falciparum with IC50 values of 3.70 µg/ml and  4.06 µg/ml, respectively. In addition the flavones 3,5,7,4’-tetramethoxyflavone and 5,7,4’-trimrthoxyflavone are active against Candida albicans and Mycobacterium sp. [5]

Antiviral activity

Two flavones (5-hydroxy-7-methoxyflavone and 5,7-dimethoxyflavone) fromK. parviflora rhizome exhibited antiviral activity against HIV-1 protease with IC50 values of 19 µM. Another compound, 5-hydroxy-3,7-dimethoxyflavone inhibited HCV protease and HCMV proteaces with IC50 of 190 µM and 250 µM, respectively. [10]

Anti-inflammatory activity

Crude ethanol extract and the chloroform extract of K. parviflora rhizome yielded a number of methoxyflavonoid compounds (5,5-hydroxy-3,7,3’,4’-tetramethoxyflavone; 5,7-dimethoxyflavone; trimethylapigenin; and tetramethylluteolin) which showed anti-inflammatory activities. Results of investigations showed that the ethanol extract and 5,5-hydroxy-3,7,3’,4’-tetramethoxyflavone suppressed mRNA expression of inducible nitric oxide synthase (iNOS) in a dose dependent manner while cyclooxygenase-2 (COX-2) mRNA expression was partially affected. The other three active compounds mentioned above markedly inhibited the production of nitric oxide (NO) in lipopolysaccharide (LPS)-activated RAW264.7 cells. They moderately inhibited the production of TNF-alpha, strongly inhibited expression of iNOS mRNA and iNOS protein in a dose dependent manner, but did not inhibit p-ERK or p-JNK protein expression. There was no inhibition of the enzyme activity of inhibitor of kB kinases nor mitogen-activated protein kinases by trimethylapigenin but it inhibited the activity of spleen tyrosine kinase (SYK). The results suggested that the anti-inflammatory activity of K. parviflora rhizome is due to the inhibition of iNOS mRNA expression, COX-2 mRNA expression and inhibition of SYK which may be involved in the suppression of LPS-induced signaling in macrophages. [13] [14]

Hepatoprotective activity

Amongst the isolates of the K. parviflora rhizome, 5,3’-dihydroxy-3,7,4’-trimethoxyflavone showed high hepatoprotective activity compared to the commercial agent silybin with IC50 value of 18.4 µM and 38.8 µM, respectively when tested on D-GalN-induced cytotoxicity in primary cultured mouse hepatocytes. [15]

Cytochrome P450 enzymes activity

The extract of K. parviflora influenced the hepatic CYP450 metabolic enzymes including CYP1A1, CYP1A2, CYP2B and CYP2E1 activities by non-competitive, mixed-competitive, competitive and uncompetitive mechanisms, respectively in in vitro studies using non-induced mouse hepatic microsomes.  In addition, K. parviflora (250 mg/kg) administered orally to mice for duration of 7, 14 and 21 days significantly induced CYP1A1, CYP1A2, CYP2B, CYP2E1 enzyme activities in different manners. CYP3A enzyme activity was not affected by the extract. Hence, the extract utilization with other herbs or drugs showed potential drug-herb interactions. [16]

Cardiogenic activity

The extract of K. parviflora rhizome showed positive effect on the nitric oxide (NO) signaling pathway resulting in decreased defibrillation efficacy. It was found that the extract increased the cyclic guanosine monophosphate (cGMP) level and decreased cardiac function and Calcium (Ca) transient and this influence the physiology of normal heart via the attenuation of cardiac function and the reduction of Ca transient in ventricular myocytes in rat models. High K. parviflora extract concentration attenuated defibrillation efficacy and increased cardiac vulnerability to arrhythmia in the normal swine heart. [17] [18]

Vasorelaxation activity

Ethanol extract of K. parviflora rhizome showed the ability to induce vasorelaxant activities when tested for preliminary studies. The vasorelaxant activity was found to be inhibited by the removal of endothelium, by N(G)-nitro-l-arginine and by 1H-[1,2,4] oxadiazolol [4,3-a]quinocaline-1-one. At the same time the extract was found to inhibit contractile response to exogenous Ca2+. [20]

Two compounds isolated from the K. parviflora  rhizome namely 5,7-dimethoxyflavone (DMF) and 3, 5, 7, 3', 4'-pentamethoxyflavone (PMF) exhibited the vasorelaxant activity when tested on isolated aortic rings of rat and on isolated human cavernosum, respectively. DMF caused relaxation of the aortic ring of rats in a dose dependent manner. The process believed to be partially mediated by NO-cGMP and cycloxygenase pathway and is due in the main to increasing K+ efflux, and inhibition of Ca2+ influx from the extracellular space. Meanwhile PMF showed weak effects on the release of NO and had no effect as a K(ATP)- or K(Ca) channel opener, a phosphodiesterase inhibitor, a stored-operated Ca2+ channel blocker or a Rho-kinase inhibitor. It is believed that PMF’s vasorelaxant activity of human cavernosum is through voltage-dependent Ca2+ channels and other mechanisms associated with calcium mobilization. [19] [21]

Antispasmodic activity

Ethanol extract of K. parviflora rhizome has the capability of relaxing the phenylephrine-precontracted aortic ring and antispasmodic activity in the ileum when it was precontracted with acetylcholine in a dose-dependent manner. [26]

Improvement of blood fluidity

The active principle of K. parviflora rhizome extract (methoxyflavones) showed to be responsible in improving the fluidity of blood by its ability to reduce blood passage time through a micro slit using a disseminated intravascular coagulation model. This is attributed to the activation of fibrinolysis, demonstrated by elongation of the euglobulin lysis time and an in-vitro fibrinolysis assay. [22]

Antigastric ulcer activity

Ethanol extract of K. parviflora rhizome administered orally to indomethacin, HCl/EtOH and water immersion-induced gastric ulcer formation showed gastroprotective activity partly due to preservation of gastric mucus secretion and not related to inhibition of gastric acid secretion. [25]

Anticholinesterase activity

The extract of the K. parviflora rhizome exhibited significant acetycholinesterase and butrylcholinesterase inhibitory activity. Two methyl-flavones namely 5,7,4’-trimethoxyflavone  and 5,7-dimethocyflavone were identified to have the highest potential inhibitory activity specific to each enzyme with the percentage inhibitory activity varying over 43-85%. They are specifically inhibited acetylcholinesterase and butrylcholinesterase, respectively. [27]

Antixanthine oxidase activity

The extract of K. parviflora rhizomes showed potent antixanthine oxidase activity with 38% inhibition at 500 µg/ml against xanthine oxidase (XOD). Two methoxyflavones isolated from extracts of K. parviflora rhizome namely are 3,5,7,4’,5’-pentamethoxyflavone and 3’,4’,5,7-tetramethoxyflavone showed inhibitory activity with IC50 value of 0.9 and >4 mM, respectively. These two compounds effected their action via competitive/non-competitive mixed type. [28]

Antioxidant activity

Ethanol extract of K. parviflora was amongst the plants investigated for their antioxidant activity and proved to exhibit potent antioxidant activity by the 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS) method and in vitro study by thiobarbituric acid-reactive substance (TBARS) assay in pooled plasma of diabetic patients. The K. parviflora extract also was found to reduce superoxide generation and increases nitrite levels in aortae of streptozotocin-induced diabetic rats. [29][30]

Sexual behavioural activity

K. parviflora extract has been seen to increase in libido and sexual performance in rats and mice. These effects do not affect the size and weight of testes. The significant increase in serum testosterone as seen in one study was attributed more to the ability of the extract to enhance circulation to the testes. The testosterone-like effect does not disturb the hypothalamic-pituitary-testicular axis as K. parviflora did not affect the levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), progesterone and corticosterone levels in blood of animals treated with the extracts. The 7-methoxyflavone group of compoundsisolated from K. parviflora showed inhibitory activity on phosphodiesterase type 5 (PDE5) and phosphodiesterase type 6 (PDE6), suggested its importance in treatment of erectile dysfunction. 5,7-dimethoxyflavone was found to be the most potent  on PDE5 with IC50 value of 10.64 ± 2.09 μM and 3,5,73’,4’-pentamethoxyflavone was the most potent  PDE6 inhibitor with IC50 value of 7.83 μM while their IC50 value for inhibitory selectivity (PDE6/ PDE5) were 3.71 μM and 0.16 μM, respectively. [31][32][33][34][35][36]

Antiallergic activity

Ethanol extract of K. parviflora showed the most potent anti-allergic activity against antigen-induced -hexosaminidase release as a marker of degranulation in RBL-2H3 cells in a screening exercised in the Zingiberacea familywith IC50 value of 10.9 µg/ml [37].  Through another  studies it was found that several methoxyflavone exhibited anti-allergic activity and amongst the most potent is 5-hydroxy-3,7,3’,4’-tetramethoxyflavone, followed by 5-hydroxy-7-methoxyflavone and 5-hydroxy-7,4’-dimethoxyflavone. The activity is due to inhibition of cell degranulation by the mentioned compounds involving the inhibition of Ca2+ influx to the cells [38].

Antitumour activity

K. parviflora rhizome showed treatment potential for HL-60 cells, human promonocytic leukaemia U937, KB cell line, human cholangiocarcinoma (HUCCA-1 and RMCCA-1) and NCI-H187 cancer cell lines. The general features of the effects are decrease in cell growth and viability. Microscopic studies showed deformed cell morphology with condensed nuclei and apoptotic bodies. The mitochondrial transmembrane potential (MTP) was decreased. There is also activation of the caspase-3 in these cells. It was found that methoxyflavones were responsible for these actions, and the most active being 5,7,4-trimethoxyflavone. [39][40][41][42][43]

Antimultidrug resistance activity

Ethanol extract of the K.parviflora rhizome exhibited capability of increasing the accumulation of rhodamine 123, daunorubicin, calcein, and P-gp substrates in LLC-GA5-COL150 and A549 cells. The effect is dose and time dependent. The activity is related to the presence of methoxyflavones in the K.parviflora used. 5,7-methoxyflavone was the most potent inhibitor of MRP (multiple-drug resistance proteins) function. In addition, 5,7-dimethoxyflavone and 3,5,7,3’,4’-pentamethoxyflavone decreased resistance to doxorubicin in A549 cells. [44][45]

Toxicities

No documentation

Clinical Data

Antifatigue activity

A clinical trial using a randomized, double-blind, crossover design was conducted to test on the acute effects of K. parviflora rhizome on fatigue amongst college students. Results did not show any improvement on exercise performance. However, another test done on prolonged intake of K. parviflora rhizome (8-weeks) showed increase performance in 30-second chair stand test and 6 minute walk test. [23] [24]

No documentation

Adverse Effects in Human:

No documentation

Used in Certain Conditions

Pregnancy / Breastfeeding

No documentation

Age Limitations

Neonates / Adolescents

No documentation

Geriatrics

No documentation

Chronic Disease Conditions

No documentation

Interactions

Interactions with drugs

It has been found that extracts of K. parviflora altered the group of hepatic CYP450 metabolizing enzymes especially CYP1A1, CYP1A2, CYP2B and CYP2E1 by non-competitive, mixed-competitive, competitive and uncompetitive mechanism respectively. This activity raises concern over the possibility of drug-herb and herb-herb interactions. [16]

Patients with arrhythmias should avoid using this herb for fear of potential of an attack. [17]

Interactions with Other Herbs / Herbal Constituents

No documentation

Contraindications

Contraindications

No documentation

Case Reports

No documentation

References

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  2. Asiatische Heilkräuter und Heilpflanzen. Kaempferia parviflora. [homepage on the Internet]. c2008. [cited 2015 Jun 04] Available from:  http://www.siamherba.net/heilkraeuter-und-heilpflanzen/heilpflanze-h-bis-z/kaempferia-parviflora/index.html
  3. Hooker JD., Flora of British India Volume 6 L. Reeve & Co. Ltd., Ashford 1894 pg. 221
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