Genomic and in vivo evidence of synergy of a herbal extract compared to its most active ingredient: Rabdosia rubescens vs. oridonin

Abstract

Abstract. Rabdosia rubescens is a herbal root extract of traditional Chinese medicine (TCM) used to treat inflammatory diseases and oral cancers. a key principle of tcm is that multiple ingredients in a plant extract are more effective and less toxic than a single purified active ingredient or a purified drug derived from a plant product. Rabdosia rubescens extract (RRE) contains terpenoids and flavonoids, but the most active ingredient within the extract attributed to the inhibition of cancer is the kaurene diterpene, oridonin. in order to research synergy with a complete plant extract, the effects of rrE on the inhibition of prostate cancer cell proliferation were compared to the effects of pure oridonin alone in vitro. three groups of 8 Scid mice bearing human prostate cancer xenografts (lapc-4) were administered either rrE containing 0.02 mg/g oridonin, pure oridonin at a dose of 0.02 mg/g, or pure oridonin at a dose of 0.1 mg/g, by gavage for 5 days/week for 4 weeks. rrE and pure oridonin at 0.1 mg/g inhibited tumor growth to a similar extent, while oridonin at a dose of 0.02 mg/g did not. Therefore, in comparison to RRE, five times more pure oridonin was required to obtain equivalent prostate xenograft growth inhibition. Since the nuclear factor-κB signaling pathway and inflammation are implicated in prostate carcinogenesis, gene microarray analysis was conducted and demonstrated activation of genes by rrE that was not evident with oridonin treatment alone. this study demonstrated that genomic methods and xenograft studies are capable of demonstrating the benefits of the synergy of whole plant extracts rather than active ingredients isolated and purified as drugs. IntroductionBotanical extracts are used for the prevention and treatment of common conditions by 80% of the world's population according to estimates made by the World health Organization (1). drugs are produced from botanical sources by isolation and purification of the most active ingredients, while other substances in the raw fraction are separated. Synergistic interactions of mixtures of bioactive constituents and related substances or analogs in plant extracts have been proposed to occur with the most active ingredient. these interactions help explain the improved effectiveness of extracts containing multiple ingredients compared to drugs developed from single constituents.We previously studied the action and metabolism of chinese red yeast rice (Monascus purpureus Went) (crYr), a dietary supplement containing monacolins, one of which (monacolin K) is identical in structure to the statin drug lovastatin, and to unsaturated fatty acids and phytosterols capable of lowering low-density lipoprotein (ldl) cholesterol in humans (2-5). the apparent bioactivity of crYr containing 6 mg of Monacolin K was equivalent to 20 mg of purified lovastatin. moreover, crYr is well tolerated in patients who are intolerant to statin drugs (6), suggesting that the lower amounts of active substances, enhanced action and more complete metabolism in comparison to a d...

Nigella sativa as an anti-inflammatory and promising remyelinating agent in the cortex and hippocampus of experimental autoimmune encephalomyelitis-induced rats

“…A key principle of traditional Chinese medicine is that multiple ingredients in a plant extract are more effective and less toxic than a single purified active ingredient or a purified drug derived from a plant product (Wong et al, 2010). Based on this concept, the whole N. sativa seed was the choice in this study to be less toxic, easy to administrate and more effective than its single purified active ingredients.…”

Oridonin induces apoptosis through the mitochondrial pathway in human gastric cancer SGC-7901 cells

“…Research showed that oridonin was one of the most important antitumor active ingredient of Rabdosia rubescens (33)(34)(35)(36). Our previous studies showed that oridonin could arrest the cell cycle in G 2 /M phase in human gastric cancer SGC-7901 cells (3).…”

Selection for High Oridonin Yield in the Chinese Medicinal Plant Isodon (Lamiaceae) Using a Combined Phylogenetics and Population Genetics Approach

“…H. Hara [12], [13]. In fact, the majority of recent studies that evaluate the bioactivity of oridonin have focused on I. rubescens as the source of the compound [10], [14]–[16].…”