Flavonoids and their glycosides, including anthocyanins

Artocarpus: A review of its traditional uses, phytochemistry and pharmacology

N-Acetyl-p-aminophenol (APAP) or acetaminophen is the most common drug ingredient worldwide. It is found in more than 600 different over-the-counter and prescription medicines. Its long-term and overdose use is highly toxic and may result in liver injury. Thus, this study was designed to assess the preventive effects and to suggest the mechanisms of action of the navel orange peel hydroethanolic extract, naringin, and naringenin in APAP-induced hepatotoxicity in male Wistar rats. APAP was administered to male Wistar rats at a dose level of 0.5 g/kg body weight (b.w.) by oral gavage every other day for 4 weeks. APAP-administered rats were treated with the navel orange peel hydroethanolic extract (50 mg/kg b.w.), naringin (20 mg/kg b.w.), and naringenin (20 mg/kg b.w.) by oral gavage every other day during the same period of APAP administration. The treatments of APAP-administered rats with the peel extract, naringin, and naringenin produced a significant decrease in the elevated serum AST, ALT, ALP, LDH, and GGT activities as well as total bilirubin and TNF-α levels while they induced a significant increase in the lowered serum albumin and IL-4 levels. The treatments also resulted in a significant decrease in the elevated liver lipid peroxidation and enhanced the liver GSH content and SOD, GST, and GPx activities as compared with APAP-administered control; the peel extract was the most potent in improving the liver LPO, GSH content, and GPx activity. In addition, the three treatments significantly downregulated the elevated hepatic proapoptotic mediators p53, Bax, and caspase-3 and significantly upregulated the suppressed antiapoptotic protein, Bcl-2, in APAP-administered rats. In association, the treatments markedly amended the APAP-induced liver histopathological deteriorations that include hepatocyte steatosis, cytoplasmic vacuolization, hydropic degeneration, and necrosis together with mononuclear leucocytic and fibroblastic inflammatory cells’ infiltration. In conclusion, the navel orange peel hydroethanolic extract, naringin, and naringenin may exert their hepatopreventive effects in APAP-administered rats via enhancement of the antioxidant defense system and suppression of inflammation and apoptosis.

The Preventive Effects and the Mechanisms of Action of Navel Orange Peel Hydroethanolic Extract, Naringin, and Naringenin in N-Acetyl-p-aminophenol-Induced Liver Injury in Wistar Rats

Prenylated flavonoids are a large group of compounds that combine a flavonoid skeleton with a lipophilic prenyl side-chain. The-side chain may be modified, especially by oxidation, and this variation contributes many structural possibilities. Combining the flavonoid skeleton with a lipophilicity of the prenyl side-chain gives the resultant great potential for biological activity. The cytotoxic activity of prenylated flavonoids has been reviewed with the aim of evaluating the potential of these compounds for further research. The search for activity has been restricted to from blood derived cells to limit the number of sources cited and get a more valuable comparison of the compounds. All sources touching on the potential toxicity of prenylated flavonoids on blood-cell lines in last 30 years of research have been cited in this review. The Sciencedirect, Web of Knowledge, Scifinder, and Reaxys databases were searched for reports, descriptions, and structural information prenylated flavonoids. A wide spectrum of cell lines, coupled with the presence and/or sometimes the absence of a standard cytotoxic compound used to compare effects made the evaluation of data more difficult. An attempt to identify each structure–activity relationships was made. Although the toxicity of the compounds described here does not usually reach the nanomolar range of concentration for leukemic cancer cell lines, the prenylated flavonoids may possess a strong advantage, in that they are relatively non-toxic to non-cancer cells. Some possible mechanisms of action for the cytotoxicic effect have also been described.

Cytotoxic potential of C-prenylated flavonoids

The plant kingdom harbours many diverse bioactive molecules of pharmacological relevance. Temperate fruits and vegetables have been highly studied in this regard, but there have been fewer studies of fruits and vegetables from the tropics. As global consumers demand and are prepared to pay for new appealing and exotic foods, tropical fruits are now being more intensively investigated. Polyphenols and major classes of compounds like flavonoids or carotenoids are ubiquitously present in these fruits, as they are in the temperate ones, but particular classes of compounds are unique to tropical fruits and other plant parts. Bioactivity studies of compounds specific to tropical fruit plants may lead to new drug discoveries, while the synergistic action of the wide range of diverse compounds contained in plant extracts underlies nutritional and health properties of tropical fruits and vegetables. The evidence for in vitro and animal bioactivities is a strong indicator of the pharmacological promise shown in tropical fruit plant biodiversity. In this review, we will discuss both the occurrence of potential bioactive compounds isolated and identified from a selection of tropical fruit plants of importance in Australia, as well as recent studies of bioactivity associated with such fruits and other fruit plant parts.

Major Australian tropical fruits biodiversity: bioactive compounds and their bioactivities.

A new oxepinoflavone, artoindonesianin E1 (1), was isolated from the wood of Artocarpus elasticus, along with four known prenylated flavones: artocarpin (2), cycloartocarpin (3), cudraflavones A (4) and C (5). The structure of the new compound was identified by spectroscopic methods. Upon cytotoxic evaluation against murine leukemia P-388 cells, the new compound showed IC50 5.0 μg/mL.

/pdf/an-oxepinoflavone-from-artocarpus-elasticus-with-cytotoxic-5gppx32rsa.pdf

An oxepinoflavone from Artocarpus elasticus with cytotoxic activity against P-388 cells.

Artocarpus, locally known as “nangka-nangkaan”, is one of the important genera of family Moraceae. The plants belong to this genus grow endemically and also cultivated throughout Indonesian region. In this study, a phytochemical study on three species of Artocarpus, namely A. heterophyllus, A. elasticus and A. lanceifolius, has been carried out, and the biological effects of the isolated compounds against Plasmodium palcifarum strain K1 and 3D7 have been evaluated. The phytochemical investigation of these plants resulted, three new prenylated flavones, trivially named artoindonesianin E-1 (1), artoindonesianin Z-4 (2) and artoindonesianin Z-5 (3), beside seventeen known prenylated flavones. Antimalarial effect of some selected isolated flavone derivatives showed that artonin E exhibited very strong inhibition (IC50 0.1 mg/mL) against K1 strain in comparison against 3D7 strain of Plasmodium falciparum (IC50 0.3 mg/mL). A related prenylated flavone, namely 12-hydroxyartonin E, exhibited strong inhibition (IC50 0.9 mg/mL) against K1 strain, but weak inhibition (IC50 14.3 mg/mL) against 3D7 strain. Those two compounds were the member of 3-prenylflavone type. In addition, the other isolated flavone derivatives showed moderate inhibition with IC50 respectively 2.1, 1.6, 3.6, 1.3, 6.7 and 2.1 mg/mL against both the strain of P. falciparum, except for flavanone-3-ol derivative (dihydromorin), which had no inhibition.

Prenylated flavones from some Indonesian Artocarpus and their antimalarial properties.

New prenylated flavones, artoindonesianins Z-4 and Z-5, together with four known prenylated flavones, artonin E, 12-hydroxyartonin E, artobiloxanthone, and cycloartobiloxanthone, have been isolated from the methanol extract of the tree bark of Artocarpus lanceifolius. The structures of these compounds were determined on the basis of spectroscopic data, including UV, IR, 1D and 2D NMR, and mass spectra. The cytotoxic effect of the isolated compounds against murine leukemia P-388 cells is described.

https://journals.sagepub.com/doi/pdf/10.1177/1934578X0900400710

Prenylated flavones from Artocarpus lanceifolius and their cytotoxic properties against P-388 cells.

Objective : This research aims to determine the dose of Indonesian velvet bean ( Mucuna pruriens ) extract which has significant effect on the fertility mice (concentration, motility and morphology of mice sperm). The extract is expected to become an alternative infertility herbal medicine relatively more secure and affordable replacing synthetic hormonal drugs which tend to have negative effects. Methods : The seed was taken from Yogyakarta Indonesia. Fertility test was done to fertile adult male albino mice 12 w old, weighing 25-35 grams. Fertility tests performed on seven groups of mice; i.e. negative control, positive control and treatment groups (five dose levels at 50, 100, 150, 200 and 250 mg/kg body weight). Subsequent fertility test results were statistically tested, including tests of normality (Kolmogorov-Smirnov) followed by T test (Independent-Samples T Test). Results: The sperm concentration and motility increased as an increased dose of seed extract was admisitered, as well as decreased abnormal morphology. The highest change in the quality and quantity of sperm occurred at the dose of 250 mg/kg body weight with increased sperm concentration of about 22 million, sperm motility increased by 18% and decreased abnormal sperm morphology by 12%. Statistical analysis showed a significant increase in sperm concentration and motility at doses of 100, 150, 200 and 250 mg/kg body weight, whereas a significant decrease of abnormal sperm morphology was found at doses of 150, 200 and 250 mg/kg body weight. Conclusion : Based on this study it is concluded that Indonesian velvet beans seed extract can increase the fertility of albino male mice significantly at dose level 250 mg/kg body weight.

The effect of indonesian velvet bean extract on the fertility of albino male mice

This research was focused on pharmacological studies of antiparkinson’s activity of  Indonesian Mucuna pruriens extract in mice. Effect of ethanolic extract of Mucuna pruriens was studied using in-vivo parameters, i.e. catalepsy and transfer latency. The ethanolic extracts of Mucuna pruriens were assessed at two dose levels (200 and 400 mg/kg) in haloperidol-induced mice. The results showed that Mucuna pruriens extract decreases the cataleptic symptons and transfer latency score. The Mucuna pruriens extract at a dose level of 200 mg/kg was better than those at a dose level 400 mg/kg in reduce catalepsy and transfer latency scores. Mucuna pruriens extract were considered to be safe up to a dose level of 5000 mg/kg  based on the acute toxicology test.

Iqbal Musthapa

Papers

An oxepinoflavone from Artocarpus elasticus with cytotoxic activity against P-388 cells.

Prenylated flavones from some Indonesian Artocarpus and their antimalarial properties.

Prenylated flavones from Artocarpus lanceifolius and their cytotoxic properties against P-388 cells.

The effect of indonesian velvet bean extract on the fertility of albino male mice

EVALUATION OF ANTIPARKINSON’S ACTIVITY OF INDONESIAN VELVET BEAN (Mucuna pruriens) EXTRACT