Curcuma zedoaria Rosc (Zingiberaceae): a review on its chemical, pharmacological and biological activities

Around 80% of human population in the world relies on herbal or phytomedicines for their primary health care needs. The treatment of many diseases and disorders with phytomedicines is considered and observed as very safe with no or minimal side effects. Many medicinal plants and their preparations are practised at home as remedies for treating and preventing various diseases and disorders. For example, medicinal plants and their crude parts such as tulsi, neem, turmeric and ginger are used to cure or treat several common ailments, out of which Curcuma zedoaria Rosc commonly known as white turmeric is one of the important crude drugs belonging to Zingiberaceae family and genus Curcuma. Traditionally, it has been reported to possess many biological activities been used for many therapeutic actions due to the presence of wide range of phytoconstituents in it. The main objectives of the present work are to carry out extensive review on its chemical, pharmacological and biological activities of plant. In the present review article, extensive data on its chemical, pharmacological and biological activities have been collected from various online sources including indexing sites such as Web of Science, Scopus, PubMed and Research Gate and presented. Various articles published in indexed journals and other databases have been collected and reviewed systematically. The present review investigation is very much helpful for researchers and readers to collectively have valuable information on chemistry, pharmacology and biological effects of Curcuma zedoaria Rosc. The present investigation concludes that the white turmeric is found to possess complex range of phytoconstituents such as curcumin, ethyl p-methoxycinnamate, β-turmerone, β-eudesmol, zingiberene, dihydrocurcumin, furanodiene, α-phellandrene, 1–8 cineole, β-elemense and germacrone. Due to the presence of wide range of phytoconstituents, plants have been reported for its diverse biological activities.


Background
Around 80% of human population in the world relies on herbal or phytomedicines for their primary health care needs. The treatment of many diseases and disorders with phytomedicines is considered and observed as very safe with no or minimal side effects. Many medicinal plants and their preparations are practised at home as remedies for treating and preventing various diseases and disorders. For example, medicinal plants and their crude parts such as tulsi, neem, turmeric and ginger are used to cure or treat several common ailments, out of which Curcuma zedoaria Rosc commonly known as white turmeric is one of the important crude drugs belonging to Zingiberaceae family and genus Curcuma. Traditionally, it has been reported to possess many biological activities been used for many therapeutic actions due to the presence of wide range of phytoconstituents in it [1]. Many researchers have been scientifically worked on various chemical and biological investigations of white turmeric and they have published research papers in various journals and in scientific databases. Literature search revealed that, till date, no reports have been published on its extensive review about chemical, pharmacological and biological activities of white turmeric. Hence, there is solid need to have collective information about chemical and biological database of plant which will be helpful to other researchers and readers. With respect to this need, we have made an attempt to carry out the present review work.

Methodology for data collection
In the present review article, extensive data on its chemical, pharmacological and biological activities have been collected from various online sources including indexing sites such as Web of Science, Scopus, PubMed and Research Gate and presented. Various articles published in indexed journals and other databases have been collected and reviewed systematically.

Anti-venom activity
Lim et al. have reported anti-venom activity of extract of white turmeric. It inhibits activity effect on binding of anti-cobra antibody venom to antigen, cobra venom, in the modification of enzyme-linked immune sorbent assay (ELISA). Extract produces toxin activity extending concentration time of diaphragm muscle after envenomation and had a potency to protect cellular proteins from venom degradative enzymes [2]. Chaveerach et al. have reported antidote activity from extract of C. zedoaria Rosc against cobra antidote. The plant material collected and kept it for DNA extraction by TAB procedure and appropriate DNA concentration were determined by using UV (160A) and DNA was extracted by PCR with ISSR primers [17].

Anti-fertility activity
Nicolas Xavier Ongako et al. have reported anti-fertility activity from ethanol extract of C. zedoaria Rosc on seminiferous tubule cells in rat testis. They have observed decreases in number of spermatogenic cell layer and mitosis count in administration of white turmeric rhizome with p value < 0.05. Study has reported rhizomecontaining curcumin has good anti-fertility effect in rats [18].

Hypotensive activity
Lim et al. have reported the hypotensive effect of C. zedoaria Rosc on endothelium in hypertensive rats and results were compared against Captopril as standard agent [2].

CNS depressant activity
Lim et al. have reported CNS depressant activity from extract of methanol of C. zedoaria Rosc. They have isolated germacrone, curzerenone and germacrone epoxide and investigated for its CNS depressant effect [2].

Insecticidal activity
Lim et al. have reported insecticidal activity of C. Zedoaria Rosc oil for its significant larvicidal activity against the two mosquito species [2]. Phukerd [25].

Anti-platelet activity
Kim et al. have studied the pharmacological effects of white turmeric in their investigation. They have studied the anti-inflammatory, antitumor, antibacterial, immunological activity, cytotoxic and antifungal activity. They also have studied the in vitro inhibitory effect in collagen, platelet activation factor (PAF)-induced platelet aggregation [26]. The extract of different concentrations was added to gel formed and decrease in crystal size was measured for 5 days using travelling microscope [27].

Anti-ulcerogenic activity
Lim et al. have reported extracts of C. Zedoaria Rosc for its anti-ulcerogenic effect in stress-induced ulcer in mice. The n-hexane soluble fraction was found to be more effective than methanol soluble fraction. The effect was comparable to that of standard drug Omeprazole [2].

Hepatoprotective activity
Lim et al. have reported the sesquiterpenoids furanogermenone isolated from C. Zedoaria Rosc for its hepatotoxic activity in carbon tetrachloride-induced liver lesion in mice [2]. Marikawa et al. have studied the hepatoprotective effect of 80% aqueous acetone extract of C. zedoaria Rosc rhizome against D-galactosamine/ lipopolysaccharide-induced acute liver injury in mice. They have reported potent protective effects of sesquiterpenes and curcumin from c. zedoaria rhizome in mice [29]. Dilpreet Singh has reported that essential oil obtained from C. zedoaria for its hepatoprotective activity and also they have compared bioavailability with that of conventional formulation [30].

Immunomodulatory effect
Faradilla et al. have reported that polysaccharide from C. zedoaria Rosc rhizome has good antitumor activity against sarcoma 180 cells and is able to increase macrophage activity in vitro at dose 300 mg/kg indicating its immunostimulatory effect [31].

Xu et al. have studied polysaccharides of C. zedoaria
Rosc for its wound healing effects on a diabetic rat model with platelet-rich plasma exosomes assembled on chitosan/silk hydrogel sponge [33].

Antiviral activity
Lakshmi Narayanan Venu et al. have isolated Germacrone and Curcumin from C. zedoaria Rosc. rhizome and studies for antiviral activity against H 1 N 1 , HSV-1 which showed good antiviral potentials [36].

Anti-diarrhoeal activity
Md. Golam Azam et al. have induced diarrhoea by castor oil in mice and they investigated that the onset of diarrhoea was significantly prolonged by administration of ethanol extract of leaves of C. zedoaria Rosc in dose-dependent manner in 3 h and amount of stool was also decreased by ethanolic extract as compared to control animal [37].

Antipyretic activity
Gina Batoy Barbosa et al. have studied the ethanol extract of white turmeric for its antipyretic effect using the Brewers yeast administered fever inducing method and results of investigation suggested that extract showed good antipyretic effect [38]. leiomyomal cell proliferation was inhibited by treatment with extracted components [40].

Analgesic activity
Marina Silalahi et al. have studied analgesic effect of ethanolic extract of white turmeric. The mild analgesic effect has been reported on the basis of writhing inhibition. They also have investigated ether extract of rhizome, leaves and stems with moderate analgesic activity based on writhing inhibition method [11]. Lim et al. have studied analgesic effect of methanolic extract of white turmeric rhizome using acetic acid-induced writhing assay. They have also investigated petroleum ether extracts of rhizome, leaves and stem for its moderate analgesic activity with writhing inhibition assay [2].

Anti-inflammatory activity
Arif Ullah et al. have studied anti-inflammatory effect of ethanolic extract of Curcuma zedoaria Rosc against carrageenan-induced inflammation in rat paw model. Diclofenac sodium was used as standard agent and compared against control groups [41]. Marina Silalahi et al. have studied anti-inflammatory effect of petroleum ether and chloroform extract of rhizomes of Curcuma zedoaria Rosc. The results of investigation showed that test samples showed P < 0.001 when compared to standard drugs with respect to its anti-inflammatory effect. The petroleum ether extract at 200 mg/kg and chloroform extract at 400 mg/kg showed maximum anti-inflammatory effect [11]. Angel et al. have studied anti-inflammatory activity of extract of Curcuma zedoaria Rosc in rats. In their study, they have administered 0.1 ml of 1% w/v solution of carrageenan on right hind paw and the inflammation assessed as difference between zero-time linear circumference of injected paw, percentage of inhibition of oedema were calculated. The anti-inflammatory effect of extract was evaluated as degree of oedema inhibition [42]. Moshiurr Rahaman et al. have studied anti-inflammatory activity of methanolic extracts of white turmeric C. Zedoaria Rosc in albino rats. The results of investigation were compared with standard drug indomethacin [43].

Antioxidant activity
Sudipta et al. have investigated antioxidant activity of essential oil of extracts obtained from rhizomes of white turmeric using DPPH, ABTS and reducing power assay by scavenging method [3].  [58]. Quan-Qian Mao has reported that Curcuzedoalide isolated from white turmeric showed inhibition of cell proliferation in AGS cells induces apoptosis [59]. Tomas Zarybnicky et al. have reported Germacrone a natural molecule extracted and isolated from white turmeric for its anticancer activity against breast cancer, liver cancer and glioblastoma cell [60].

Conclusions
The present review concludes that white turmeric is one of the very important traditional herbal medicines. Traditionally, plant and its extracts have been used for management of various illnesses in human beings. Various parts of plant have been reported for the presence of complex phytoconstituents which include curcumin, ethyl p-methoxycinnamate, β-turmerone, β-eudesmol, zingiberene, dihydrocurcumin, furanodiene, α-phellandrene, 1-8 cineole, β-elemene and germacrone. The reports on scientific validation of white turmeric on its biological and other pharmacological effects showed that plants have good number of biological activities which include antimicrobial, anticancer, analgesic, antipyretic, antiviral, antioxidant, wound healing, antiinflammatory, insecticidal activity and cardioprotective activities.