Ethnomedicine: A Source of Complementary Therapeutics

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Debprasad Chattopadhyay et al.

of these compounds are critical to their activity. The Centella asiatica L., Maclura cochinchinensis Cornor, and Mangifera indica L. used as herpesvirus remedies in Thailand can inhibit HSV-1 and HSV-2 virion production in plaque inhibition assay. Combinations of each of these extracts with acyclovir resulted in synergistic or additive interaction in a dose dependent manner, probably due to the active constituent asiaticoside of C. asiatica and mangiferin of M. indica with good therapeutic potential [Yoosook et al., 2000]. Bunyapraphatsara et al., 2000 reported that the morin, a flavonoid group, isolated from ethyl acetate extract of Maclura cochinchinensis have powerful anti-HSV-2 activity (EC50 38.553.5µg/ml), due to their free hydroxyl groups. The extract of Rhus succedanea and Garcinia multiflora containing amentoflavone and robustaflavone, inhibits in vitro growth of HSV, while VZV were inhibited by rhusflavanone and succedaneflavanone [Chattopadhyay, 2006]. It was reported that the quercetin from Caesalpinia pulcherrima Swartz had a broad anti- herpesvirus activity (EC50 24.3-50mg/l), by inhibiting early stage of multiplication [Chiang et al., 2003], suggesting its potential use for anti-HSV drug development. Similarly the isoquercitrin of Waldsteinia fragarioides had significant anti-HSV activity [Khan et al., 2005]. When 18 flavonoids of five classes were tested against HSV-1 and HSV-2, epicatechin (EC), epicatechin gallate (ECG) and quercetin (flavanols); genistein (isoflavone) and naringenin (flavanone) showed a high level of CPE inhibitory activity. EC, ECG, galangin and kaempferol showed strong anti-HSV activity, while catechin, epigallocatechin, epigallocatechin gallate, naringenin, apigenin, chrysin, baicalin, fisetin, myricetin, quercetin, and genistein had moderate effect on HSV-1 in plaque reduction assay. Hence, flavanols and flavonols appeared to be more active than flavones, probably due to their structural differences. Furthermore, Vero cells treated with ECG and galangin before virus adsorption led to a enhancement of inhibition by yield reduction assay, indicating that an intracellular effect may also be involved [Lyu et al., 2005]. Hence, the potent antiviral flavonoids appear to block viral DNA/RNA polymerase, where the degree of inhibition depends on the structure and side chain. A recent study with ent-epiafzelechin-(4α->8)-epiafzelechin (EEE) from fresh leaves of Cassia javanica L. agnes de Wit revealed the inhibition of HSV-2 replication in a dose-dependent manner (IC50 83·8±10·9µM) by inhibiting penetration and replication at the late stage of viral life cycle [Cheng et al., 2006]. The evidence of oxidative stress in virus-infected individuals, particularly in chronic lifelong HSV infections, indicates that antioxidants like flavonoids and proanthocyanidins with low oral bioavailability may have some role in controlling disease progression [Chattopadhyay & Khan, 2008]. A recent report revealed that sodium rutin sulfate (SRS), a sulfated derivative of the flavonol glycoside rutin inhibit HSV-1 (IC50 88.3 ± 0.1 µM) at CC50 >3.0 mM in human genital ME180, HeLa and primary human foreskin fibroblast cell lines, indicating its novel candidature for the development of anti-HSV microbicide [Tao et al., 2007].


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