Avicenna Journal of Phytomedicine
Volume:11 Issue: 6, Nov-Dec 2021

It is of interest to investigate the anti-proliferative effect of β-sitosterol (BS) on human hepatocellular carcinoma (HepG2) cell line.

β-sitosterol treatments (0.6 and 1.2 mM/ml) were done in HepG2 and after 24 hr, cell viability was evaluated by MTT assay. Reactive oxygen species (ROS) accumulating potential of BS was assessed by dichloro-dihydro-fluorescein diacetate staining. Morphology related to apoptosis was investigated by acridine orange and ethidium bromide dual staining. Cytochrome c and caspase 3 expressions were evaluated by immunofluorescence and western blot analyses.

β-sitosterol induced cytotoxicity (p<0.001) and intracellular ROS in HepG2 cells in a dose-dependent manner.BS treatments accumulated induced intracellular ROS accumulation which led to membrane damage and mitochondrial toxicity. At the molecular level, BS treatments induced cytochrome c release from mitochondria and enhanced the protein expressions (p<0.05 vs 0.6 mM/ml and p<0.001 vs 1.2 mM/ml) of both caspase 3 and cleaved caspase 3.

β-sitosterol induced ROS accumulation which plays a critical role in apoptosis via the intrinsic pathway in HepG2 cells. The present investigation paves the way for further in vivo studies.

Propolis is a sticky, resinous substance produced by honeybees from various plants. Various biological properties of propolis and its extracts have been recognized in previous studies including the antiseptic, anti-inflammatory, antioxidant, antiviral, hepatoprotective, antitumor, antibacterial and antimycotic properties. This study aimed to summarize the effect of propolis on metabolic parameters in human adults using systematic review and meta-analysis.

A comprehensive systematic search was performed in ISI Web of Science, PubMed, Scopus, and Google Scholar up to July 2020 for controlled clinical trials evaluating the impact of propolis on lipid profile and liver enzyme biomarkers. A random effects model was used to calculate the weighted mean difference (WMD) and 95% confidence interval (CI) as the difference between the mean for the intervention and control groups.

The present meta-analysis included six randomized controlled trials. There was significant reduction in Aspartate Aminotransferase (AST) in comparison to the control groups (WMD=-2.01; 95% CI: -3.93--0.10; p=0.039). However, a non-significant effect was observed in Triglycerides (TG), Total cholesterol (TC), low-density lipoprotein (LDL), High-density lipoprotein (HDL) (WMD=-0.05 mg/dl; 95% CI: -0.27-0.18; p=0.688; WMD=7.08 mg/dl; 95% CI: -37.31-51.46; p=0.755; WMD=-0.94 mg/dl; 95% CI: -6.64-4.77; p=0.747; WMD=3.14 mg/dl; 95% CI: -1.84-8.13; p=0.216, respectively).

Current meta-analysis revealed that propolis supplementation can reduce AST; nevertheless, there was no significant effect on lipid profile indices and ALT.

Previous clinical trials have suggested that herbal medicines can improve the quality of life (QOL) and survival of cancer patients. This study was aimed to evaluate the effects of a polyherbal compound (PHC, formulated as syrup) consisting of Allium sativum, Curcuma longa,Panax ginseng, and Camellia sinensis on the quality of life (QOL) and survival in patients with upper gastrointestinal cancers.

A randomized placebo-controlled trial was carried out on patients with esophageal or gastric cancer who had finished their oncological treatments. The patients were randomly assigned to PHC (n=20) or placebo (n=20) group. The PHC group was treated with the PHC for 12 weeks, while the placebo group received 70% sucrose syrup. The QOL was assessed at baseline and after 12 weeks. The patients were followed for up to 24 months to determine overall survival.

PHC significantly improved cancer-related symptoms, physical performance, and psychological and social functions of the patients (p<0.05 for all cases). Death occurred in 33 and 22% of cases in the placebo and PHC group, respectively. The mean survival time was 16.8 months (95% CI: 12.8-20.9) in the placebo group and 21.4 months (95% CI: 19.1-23.6) in the PHC group but the difference was not statistically significant.

The PHC improved cancer-related symptoms, physical performance, and psychological and social functions in patients with gastrointestinal cancers. It seems that this herbal compound has the potential to be used as a supplement in the management of cancer.

Postpartum pain (PP pain) is a common problem after vaginal delivery. Some herbs are used to reduce PP pain. Due to the anti-inflammatory properties of Triticum sativum (wheat) germ, this study was conducted to investigate the effect of wheat germ on PP pain.

This is a randomized, double-blind, placebo-controlled clinical trial performed on 90 women who had a vaginal delivery and complained of moderate to severe PP pain. The participants were randomly divided into two groups. In the intervention group, a capsule containing 500 mg of wheat germ was taken every 6 hr for 2 days and in the control group, a placebo capsule was taken in the same order.The severity of PP pain was measured before and one hour after receiving the capsule by using the Visual Analogue Scale. 

The two groups were not different in terms of pain severity before the intervention. The PP pain in women with moderate pain was significantly reduced in both groups, the reduction was greater in the wheat germ group (GEE=0.04) but this reduction was not significant. The PP pain in women with severe pain was significantly reduced in both groups, however, the reduction was significantly greater in the wheat germ group (GEE=0.63, p=0.007). Moreover, the results showed that the use of mefenamic acid in the wheat germ group was significantly lower than the control group (p=0.04). Moreover, no side effect was reported after consuming the wheat germ.

It seems that wheat germ reduces severe PP pain. Further research on this plant is recommended.

Natural compounds can act as metal chelators and oxygen free radical scavengers, which allows them to be used as bioactive antagonists to heavy metals neurotoxicity. The aim of the study to analyze the morphometric effects of Coriandrum sativum (C. sativum) on lead-induced neurotoxicity. Forty Sprague-Dawley albino rats were divided into four equal groups (ten in each group): control group; coriander group: received aqueous C. sativum extracts (600 mg/kg BW for 60 days orally); lead (Pb) group: received a daily dose of lead acetate (Pb) (10 mg/kg BW for 60 days orally); Pb+ coriandrum group: received: aqueous C. sativum extract (600 mg/kg BW) prior to 10 mg/kg BW of Pb. The following parameters malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) were measured. Layers thickness and nuclei density were analyzed. Lead levels in blood and tissues were decreased significantly in the Pb group and those findings were corrected significantly (p=0.001) with C. sativum addition. Data exhibited an increase in oxidative stress marker MDA and a decrease in antioxidant enzymes activities (SOD, CAT, and GPx) significantly in the Pb group and those effects were reversed significantly (p=0.001) by C. sativum administration. The cerebellar cortex and all layers of the somatosensory cortex thickness and nuclei density were diminished significantly in the Pb group. The morphometrical measurements were corrected significantly (p=0.001) by C. sativum. From the findings of the current study, Pb caused noticeable structural and functional variations in the cerebellar cortex and somatosensory cortex. C. sativum corrected these parameters as it possesses chelating and antioxidant potentials.

Quercetin is one of the most popular flavonoid with protective effects against neural damages in Parkinson's disease (PD). We assessed the effect of quercetin administration on memory and motor function, hippocampal ‎ oxidative stress and brain-derived neurotrophic factor (BDNF) level in a 6-OHDA-induced Parkinson's rat model.

The animals were divided into the following five groups (n=8): control, sham-surgery (sham), lesion (PD), and lesion animals treated with quercetin at doses of 10 (Q10) and 25 (Q25) mg/kg. For induction of a model of PD, 6-OHDA was injected into the striatum of rats. The effects of quercetin were investigated on spatial memory, hippocampal BDNF and malondialdehyde (MDA) levels, and total antioxidant capacity (TAC). Spatial memory was assessed by Morris water maze test, and the neuronal firing frequency in hippocampal dentate gyrus (HDG) was evaluated by single-unit recordings.

Mean path length and latency time, rotational behavior and hippocampal MDA concentration were significantly increased, while time spent in the goal quadrant, swimming speed, spike rate, and hippocampal levels of TAC and BDNF were significantly decreased in the PD group compared to the sham group (p<0.01 to p<0.001). Quercetin treatment significantly enhanced time spent in goal quadrant (p<0.05), swimming speed (p<0.001) and spike rate (p<0.01), improved hippocampal TAC (p<0.05 to p<0.001) and BDNF (p<0.01 to p<0.001) level, and decreased mean path length (p<0.001), latency time (p<0.05 to p<0.001), rotational behavior and hippocampal MDA concentration (p<0.05).

The cognitive-enhancing effect of quercetin might be due to its antioxidant effects in the hippocampus.

Oxidative stress has pernicious effects on the brain. Pinus eldarica has antioxidant properties. We explored neuroprotective effect of P. eldarica against pentylenetetrazole (PTZ)-induced seizures.

Male mice (BALB/c) were grouped as control, PTZ, Soxhlet (Sox) 100, Sox 200, Macerated (Mac) 100 and Mac 200 groups. Sox and Mac extracts (100 and 200 mg/kg) were injected during 7 days. Delay in onset of minimal clonic seizure (MCS) and generalized tonic- clonic seizure (GTCS) was measured. Number of dark neurons (DN) and levels of oxidative stress indicators in the hippocampus were evaluated.

Onset of MCS and GTCS was later in groups treated with the extracts than the PTZ group (p<0.01 and p<0.001). Number of DN in the hippocampus in the PTZ group was higher than the control group (p<0.001) while in the extract groups, was lower than the PTZ group (p<0.05, p<0.01 and p<0.001). MDA level was higher whereas total thiol level and activity of SOD and CAT were lower (p<0.001) in the PTZ group than the control group. MDA level in the Sox 100 (p<0.01), Sox 200 (p<0.001) and Mac 200 (p<0.01) groups was less than the PTZ group. Total thiol level in the Sox 200 (p<0.001), SOD in the Sox 100 (p<0.05), Sox 200, and Mac 200 and CAT in the Sox 200 (p<0.001) groups were higher than the PTZ group.  

P. eldarica prevented neuronal death and reduced seizures caused by PTZ via improving brain oxidative stress.

The most important toxicity of acetaminophen is hepatotoxicity. Farnesoid X-activated receptors (FXR) are one of the nuclear receptor superfamily members which have a pivotal role in the bile acid regulation. The objective of the present study was to examine the role of FXR in mediating the hepatoprotective effects of saffron.

Male Wister rats were randomly allocated into five groups including a control, vehicle, acetaminophen and two saffron extract groups of 150 and 300 mg/kg/day. The liver function and hepatic FXR expression were evaluated using biochemical assay and real time RT-PCR, respectively. Data analysis was performed using the one-way ANOVA followed by Duncan's multiple range test.

Levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) of the acetaminophen group were significantly higher than the control group whereas those of the extract-treated groups were significantly lower than those of the acetaminophen group. The real time RT-PCR findings showed a non-significant down-regulation of FXR mRNA expression, however, a dose-dependent FXR up-regulation was seen in the groups treated with 150 and 300 mg/kg of the extract for 2.67 (p=0.002) and 10.22 (p=0.0001) fold, respectively.

The main finding of the present study was that the hepatic FXR up-regulation had an important role in saffron hepatoprotective activity.

As a herbicide, paraquat is a toxic agent that has devastating effects on human health. Gallic acid, on the other hand, is a natural compound that its anti-oxidant values have been reported in previous studies. Given these, this study was designed to evaluate whether gallic acid could reduce the toxic effects of paraquat in the liver of rats.

Six groups of rats were considered in this study. Group 1 (control group), group 2 (25 mg/kg of paraquat), group 3 (paraquat-plus-silymarin), and groups 4, 5, and 6 (paraquat together with gallic acid at the doses of 25, 50, and 100 mg/kg, respectively). After treatment, biochemical, oxidative, and histopathological parameters were evaluated in the rats.

We found that as compared to the control group, while paraquat reduced the hepatic levels of anti-oxidative compounds such as vitamin C (p<0.001), superoxide dismutase (SOD) (p<0.001), and catalase (CAT) (p<0.001), the toxic agent increased the serum levels of protein carbonyl (PC) (p<0.001), malondialdehyde (MDA) (p<0.05), and IL-1β (p<0.001). Paraquat also increased (p<0.05) both serum lipid profile and liver-associated markers in the rats. Nevertheless, gallic acid not only enhanced (p<0.05) the activity of vitamin C, SOD, and CAT but also remarkably reduced (p<0.05) the serum lipid profile, as well as the oxidative and inflammatory markers in the paraquat-treated rats. Gallic acid had also ameliorating effects on the damaged morphology of hepatocytes upon paraquat treatment.

The results of this study suggested that gallic acid possesses reinforcing effects on the antioxidant defense system and could be administered to reduce the toxicity of paraquat.

Cuscuta epithymum (CE) is one of the most popular medicinal plants in the world. However, detailed information about its toxicity is not available. Hence, this study aimed to evaluate the safety profile of CE ethanolic extract in vitro and in vivo.

The extract's in vitro toxicity profile was investigated on normal fibroblast and cervical cancer cells by cytotoxicity test. In the next step, acute oral and intraperitoneal (i.p.) toxicity of the CE extract was evaluated in Wistar rats and BALB/c mice, respectively. Sub-acute oral toxicity was also examined by administering repeated oral doses of the CE extract (50, 200, and 500 mg/kg) to Wistar rats for 28 days.

The CE extract exhibited a significant cytotoxicity on both normal (IC50 0.82 mg/ml, p<0.001) and cancer cells (IC50 1.42 mg/ml, p<0.001). Acute oral administration of a single dose of CE extract (175-5000 mg/kg) did not cause mortality; however, its i.p. administration caused mortality at doses greater than 75 mg/kg (i.p. LD50 154.8 mg/kg). In the sub-acute toxicity test, no significant effects in terms of weight change, organ weights, blood chemistry, or kidney pathology were observed. However, at 200 and 500 mg/kg doses, the CE extract significantly increased liver pathological scores compared to the control group (p<0.05 and p<0.01, respectively).

CE exhibited toxicities in i.p. acute and repeated oral dose administrations. It showed identical cytotoxicity against normal and cancer cells. This herb must be prescribed cautiously by traditional medicine practitioners.