Curcumin-phospholipid complex: Preparation, therapeutic evaluation and pharmacokinetic study in rats

A novel formulation of curcumin in combination with the phospholipids was developed to overcome the limitation of absorption and to investigate the protective effect of curcumin–phospholipid complex on carbon tetrachloride induced acute liver damage in rats. The antioxidant activity of curcumin–phospholipid complex (equivalent of curcumin 100 and 200 mg/kg body weight) and free curcumin (100 and 200 mg/kg body weight) was evaluated by measuring various enzymes in oxidative stress condition. Curcumin–phospholipid complex significantly protected the liver by restoring the enzyme levels of liver glutathione system and that of superoxide dismutase, catalase and thiobarbituric acid reactive substances with respect to carbon tetrachloride treated group (P < 0.05 and <0.01). The complex provided better protection to rat liver than free curcumin at same doses. Serum concentration of curcumin obtained from the complex (equivalent to 1.0 g/kg of curcumin) was higher (C_max 1.2 μg/ml) than pure curcumin (1.0 g/kg) (C_max 0.5 μg/ml) and the complex maintained effective concentration of curcumin for a longer period of time in rat serum. The result proved that curcumin–phospholipid complex has better hepatoprotective activity, owe to its superior antioxidant property, than free curcumin at the same dose level.     

Evaluation of the hepatoprotective effect of combination between hinokiflavone and Glycyrrhizin against CCl4 induced toxicity in rats

Liver diseases are one of the fatal syndromes due to the vital role of the liver. Most of the effective treatment of liver conditions are of natural origin. Silymarin (SI) is the standard drug used for treatment of impaired liver functions. Two natural compounds possessing promising liver protection and with different chemical structures namely; the bioflavonoid hinokiflavone (HF) isolated from Junipers phoenicea family Cupressaceae and the sweet saponin Glycyrrhizin (GL) present in Glycyrrhiza glabra (liquorice) were selected for the current study. Since the two compounds are of different nature, they may act by different mechanisms and express synergistic effect. Combination of the two compounds using to dose levels were challenged with single doses of HF, GL and SI as well. The comparison was monitored via measuring serum biochemical parameters including, aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma glutamyltranspeptidase (GGT), alkaline phosphatase (ALP) and total bilirubin, tissue parameters such as MDA, NP-SH and TP, histopathological study using light and electron microscope. Protective effect on kidney was also monitored histopathologically and biochemically through observing the levels of LDH, creatinine, creatinine-kinase, urea and uric acid. The combinations of HF and GL showed protective effect more than the used single doses of HF and GL alone. However, SI was superior to the used combination in the two used doses in all the measured parameters. The liver and kidney cells appearance under normal and electron microscope showed that SI treated groups showed almost normal cells with slight toxic signs. Cells from group treated with the higher doses of the combination of HF and GL showed slight signs of intoxication under light and electron microscope indicating good level of protection. Although the combination of HF and GL expressed good protection in the higher dose, however, the combination did not exceed the protective effect of SI.     

Hepatoprotective properties of red betel (Piper crocatum Ruiz and Pav) leaves extract towards H2O2-induced HepG2 cells via anti-inflammatory,antinecrotic, antioxidant potency

BackgroundProlonged exposure of free radicals, or known as reactive oxygen species (ROS), in hepatic cells may cause oxidative stress. Without proper treatment, it can induce liver injury and fatal hepatic disease, including cirrhosis. Red betel (Piper crocatum Ruiz and Pav) is one of Indonesia’s medicinal plants that has been known to exhibit antioxidant, anti-inflammatory activities. This study aims to determine hepatoprotective effect of red betel leaves extract (RBLE) towards liver injury.MethodHydrogen peroxide-induced HepG2 cells were used as liver injury model·H₂O₂-induced HepG2 cells were treated with 25 µg/mL and 100 µg/mL RBLE. Several parameters were observed, including TNF-α level through ELISA; necrotic, apoptotic, dead, live cells; and ROS level through flow cytometry analysis; and GPX gene expression through qPCR.ResultThe study showed that treatment with RBLE were able to decrease TNF-α level; necrotic and death cells percentage; as well as ROS level. On the other hand, it were able to increase apoptotic and live cells percentage; as well as GPX gene expression. Low concentration (25 µg/mL) of RBLE treatment exhibited stronger anti-inflammatory activity as it was resulted in the lower TNF-α level and were able to switched hepatic cell death pathway from necrosis to apoptosis as shown by the shifted of apoptotic cells and necrotic cells percentage. This lead to lower death cells and ultimately improve live cells percentage. Meanwhile high concentration of RBLE (100 µg/mL) exhibited stronger antioxidant properties as indicated by lower ROS level and higher GPX gene expression.ConclusionOverall, this study was able to demonstrate hepatoprotective effect of RBLE towards liver injury model through its anti-inflammatory and antioxidant activities.     

Liver injury in COVID-19: A minireview

In December 2019, an outbreak of unexplained pneumonia was reported in Wuhan, China. The World Health Organization officially named this disease as novel coronavirus disease 2019 (COVID-19). Liver injury was observed in patients with COVID-19, and its severity varied depending on disease severity, geographical area, and patient age. Systemic inflammatory response, immune damage, ischemia-reperfusion injury, viral direct damage, drug induce, mechanical ventilation, and underlying diseases may contribute to liver injury. Although, in most cases, mild liver dysfunction is observed, which is usually temporary and does not require special treatment, the importance of monitoring liver injury should be emphasized for doctors. The risk of COVID-19 infection of liver transplantation recipients caused more and more concerns. In this article, we aimed to review the available literature on liver injury in COVID-19 to highlight the importance of monitoring and treating liver injury in COVID-19.     

Luffa echinata Roxb.-A review on its ethanomedicinal,phytochemical and pharmacological perspective

Luffa echinata Roxb. (Cucurbitaceae) is a spreading climbing herb of tremendous medicinal importance, distributed throughout Pakistan, India, Bangladesh and Northern Tropical Africa. Traditionally various parts of the plant are being used for the treatment of different ailments such as jaundice, intestinal colic, enlargement of liver and spleen, leprosy, diabetes, bronchitis, nephritis, rheumatism, cirrhosis, dropsy, anthelmintic, stomach ache, snake bite, dog bite, fever, diarrohea and hemorrhoid disorder. The plant also possesses antioxidant, analgesic, anti-inflammatory, antidepressant, anxiolytic, antiepileptic, hepatoprotective, antibacterial, antifungal, antiulcer and anticancer activity. Research has been carried out using different techniques to support most of these claims. This review is an attempt to compile an up-to-date data on its ethanomedicinal, phytochemical and pharmacological perspective.     

Development and Evaluation of Hepatoprotective Polyherbal Formulation Containing Some Indigenous Medicinal Plants

The present study explores the hepatoprotective activity of various extracts of Ferula asafoetida, Momordica charantia Linn and Nardostachys jatamansi against experimental hepatotoxicity. Polyherbal suspensions were formulated using extracts showing significant activity and evaluated for both physicochemical and hepatoprotective activity in comparison with LIV-52 as standard. Petroleum ether (60-80°), chloroform, benzene, ethanol and aqueous extracts of Ferula asafetida, Momordica charantia Linn and Nardostachys jatamansi were evaluated for hepatoprotective activity against carbon tetrachloride-induced liver toxicity in Wistar rats. Polyherbal suspensions were prepared by the trituration method using a suspending agent and other excipients. Formulation F3 has shown significant hepatoprotective effect by reducing the elevated serum enzyme levels such as glutamate oxaloacetate transaminase, glutamate pyruvate transaminase and alkaline phosphatase. These biochemical observations were supplemented by histopathological examination of liver sections. Various parameters evaluated for all formulations were within the official specifications. Experimental data suggested that treatment with formulation F3 enhances the recovery from carbon tetra chloride-induced hepatotoxicity. From these results it may be concluded that the F3 formulation (containing chloroform, petroleum ether and aqueous extracts of Ferula asafetida, petroleum ether and ethanol extracts of Momordica charantia Linn. and petroleum ether and ethanol extracts of Nardostachys jatamansi) demonstrated significant hepatoprotective activity, that might be due to combined effect of all these extracts.     

Sasa quelpaertensis leaves ameliorate alcohol-induced liver injury by attenuating oxidative stress in HepG2 cells and mice

Oxidative stress plays a crucial role in the progression of alcoholic liver diseases and substances of antioxidant property are of special interest for therapeutic purposes. We investigated the hepatoprotective effect of leaf extracts of Sasa quelpaertensis, an edible bamboo mainly cultivated in Jeju Island, South Korea. We examined the cytotoxicity of different extracts (distilled water, 20–80% EtOH) of S. quelpaertensis on HepG2 cells and their hepatoprotective effect on HepG2 cells stimulated by ethanol (800?mM, 24?h). Furthermore, we measured reactive oxygen species (ROS) production, ethanol toxicity induced cell death, and the activity of antioxidant enzymes. In in vivo experiments, liver damage was induced by oral administration of 5?g/kg ethanol with or without potent ethanol extract of S. quelpaertensis (10 or 100?mg/kg) 12?h interval for a total of 3 doses. Only 80% ethanol extract of S. quelpaertensis (SQEE80) exhibited cytoprotective effect on HepG2 cells against alcohol-induced toxicity. SQEE80 treatment (250, 500?μg/mL) in ethanol exposed HepG2 cells showed significant attenuation of ROS production and ethanol toxicity induced cell death. Furthermore, SQEE80 markedly increased the activity of antioxidant enzyme glutathione peroxidase 1 in ethanol exposed HepG2 cells compared to ethanol stimulated cells. In in vivo experiments, SQEE80 treatment evidently suppressed the alcohol-induced histopathological changes in liver, serum ethanol content, and expression of cytochrome P450 2E1. Furthermore, SQEE80 significantly reversed the reduction of glutathione level in the ethanol challenged liver. Taken together, we suggest the possibility of developing SQEE80 as a natural hepatoprotective substance in attenuating alcohol-induced oxidative stress.     

Antioxidant and hepatoprotective activities of five eggplant varieties

Eggplant is consumed throughout the world and varies in fruit color, shape, and size. In this study, five varieties of eggplant (purple colored moderate size, white-green colored moderate size, long green, green striped moderate size and pale-green colored small size, respectively, called SM1–SM5) were evaluated for total phenolic and flavonoid content, antioxidant activity and hepatoprotection against cytotoxicity of tert-butyl hydroperoxide (t-BuOOH) in human hepatoma cell lines, HepG2. Total phenolic content found in methanol extracts of SM1–SM5 ranged from 739.36 ± 1.59 to 1116.13 ± 7.30 gallic acid equivalents mg/100 g extract and total flavonoid content from 1991.29 ± 6.32 to 3954.20 ± 6.06 catechin equivalents mg/100 g extract. SM1 and SM2 which contained high total phenolic and flavonoid had better antioxidant activities than the other varieties. Pretreatment of HepG2 cells with 50 and 100 μg/mL of SM1–SM5 significantly increased the viability (p < 0.05) of t-BuOOH-exposed HepG2 cells by 14.49 ± 1.14% to 44.95 ± 2.72%. The antioxidant activities of the eggplant were correlated with the total amounts of phenolic and flavonoid (r = 0.5310−0.7961). Significant correlation was found between hepatoprotective activities and total phenolic/flavonoid content (r = 0.6371–0.8842) and antioxidant activities (r = 0.5846–0.9588), indicating the contribution of the phenolic antioxidant present in eggplant to its hepatoprotective effect on t-BuOOH-induced toxicity.     

黄皮酰胺的合成

根据推测的生源关系,以仿生路线合成了有保肝活性的植物成分黄皮酰胺。     

Hepatoprotective effects of lychee (Litchi chinensis Sonn.): a combination of antioxidant and anti-apoptotic activities

Aim of the study

Gimjeng and Chakapat lychee (Litchi chinensis Sonn.) were evaluated for hepatoprotective activity on CCl₄-induced hepatotoxicity in rats.

Materials and methods

Fruit pulp extracts of the lychees were examined for vitamin C, phenolic contents, anti-lipid peroxidation activity and hepatoprotective effect. Male Wistar albino rats were intraperitoneally injected (ip) with CCl₄ (2 ml/kg), then were orally administered (po) with silymarin (100 mg/kg), and Gimjeng or Chakapat extracts (100 and 500 mg/kg). After ten days, the rats were sacrificed and their livers were examined histopathologically and immunohistochemically. Their serum glutamate-pyruvate transaminase, glutamate-oxalate transaminase, and alkaline phosphatase activities were analyzed. Apoptotic activity of the livers was assessed quantitatively.

Results

The Gimjeng and Chakapat extracts showed the contents of vitamin C (1.2 ± 0.6 and 4.3 ± 0.1 mg/100 g) and phenolics like trans-cinnamic acid and pelargonidin-3-O-glucoside (9.80 ± 0.21 and 19.56 ± 0.4 mg GAE/g extract, respectively), and trolox equivalent antioxidant capacity (TEAC) values (11.64 and 9.09 g/mg trolox), respectively. The Gimjeng as compared to the Chakapat demonstrated a better antioxidant activity as revealed by anti-lipid peroxidation activity with the TEAC values. Administration of CCl₄ in rats elevated the serum GPT, GOT, and ALP level whereas silymarin, Gimjeng and Chakapat extracts prevented these increases significantly. Significant decrease of apoptotic cells together with restoration of morphological changes confirmed the hepatoprotective effect in the CCl₄-induced rats pretreated with the extracts.

Conclusion

Antioxidant properties of the Gimjeng and Chakapat lychees as evidenced by the vitamin C and phenolic compounds, anti-lipid peroxidation and anti-apoptosis could explain the hepatoprotective effects in CCl₄-induced hepatotoxicity.