Research Journal of Pharmacognosy
Volume:8 Issue: 1, Winter 2021

Ulcerative colitis (UC) is a chronic inflammatory bowel disease. Herbal medicines such as Persicaria bistorta, Pistacia lentiscus, Punica granatum, and Myrtus communis manifesting a variety of pharmacological properties and effects, have been widely implicated in the treatment of UC. We report a case of UC in a 42-year-old male patient.

The patient presented frequent passage of bloody stool, severe cramping, and abdominal pain. This was accompanied by fatigue, excessive mucus, and pus in the stool. He had a 12 years prehistoric diagnosis of ulcerative colitis and received conventional therapy, which yielded no improvement in the symptoms. His regimen was then switched to the Persian traditional treatment employing the “Sahj” formula (including Persicaria bistorta, Pistacia lentiscus, Boswellia frereana, Punica granatum, and Myrtus communis) for 4 months.

After 18 days of traditional therapy with “Sahj” tablet, there was a significant improvement in his UC symptoms as evidenced in the increased frequency of his bowel movements (twice daily), absence of bloating, cramping, or abdominal pain and a normal bloodless stool. A colonoscopy report and digital rectal examination 4 months post-treatment, revealed a normal perianal area, cecum, and terminal ileum. 

The results suggest that the Persian traditional “Sahj” medicine possesses pharmacological properties that render it effective in the treatment of UC and mucosal diseases. However, further clinical trials are needed to evaluate and confirm the efficacy and safety of “Sahj” therapy.

Umbelliprenin, a prenylated coumarin from different species of Ferula, has demonstrated anti-cancer effects in various types of cancer cells, but the potential molecular mechanisms for the anti-angiogenic activity of umbelliprenin in breast cancer cells have not yet been studied.  In this study, we investigated the possible molecular pathways involved in the anti-angiogenic effect of umbelliprenin in EGF and CoCl2 stimulated SKBR-3 breast cancer cells.

Effects of umbelliprenin on the changes in EGFR signaling genes (EGFR, PI3K, AKT, mTOR, S6K, 4EBP1, ERK1/2, HIF-1α, HIF-1β, VEGF, VEGFR) and proteins (VEGF/HIF-1α) expression were assayed in SKBR-3 via Quantitative PCR and Western blotting assays.

Umbelliprenin dramatically decreased the living cells in a concentration related manner (IC50=103.9 µM) and non- toxic doses of umbelliprenin IC5 and IC10 (10 and 20 µM, respectively) were used for evaluating in vitro anti-angiogenic effects. Umbelliprenin significantly reduced pro-angiogenic AKT, ERK1, ERK2, mTOR, S6K, HIF-1α, HIF-1b, VEGF and VEGFR mRNAs in EGF-treated, and  AKT, ERK2, S6K, HIF-1α, HIF-1b, VEGF and VEGFR mRNAs in CoCl2-treated cells. Umbelliprenin significantly increased anti-angiogenic 4EBP1 mRNA in EGF / CoCl2-treated cells. It significantly decreased the levels of HIF-1α and VEGF proteins, in CoCl2-treated cells.

Our findings showed that umbelliprenin exhibits anti-angiogenic effects by decreasing the expression of AKT/mTOR/MAPK angiogenesis pathways in EGF or CoCl2 treated SKBR-3 breast cancer cells.

Carvacrol is a natural antioxidant possessing various biological properties. Diphenhydramine is a first-generation antihistamine prescribed for allergies and the common cold. Recently, investigations have shown that diphenhydramine might cause genotoxicity. Antioxidants significantly act in defending cells against oxidative induced genotoxicity. Here, we assessed the protective effect of carvacrol, as a potent antioxidant, on diphenhydramine induced oxidative genotoxicity on human peripheral blood lymphocytes.

Peripheral lymphocytes were treated as followed groups: diphenhydramine concentrations (200, 500 and 1000 µg/mL), diphenhydramine in combination with carvacrol (5 µg/mL), cisplatin (0.05 µg/mL) and cisplatin in combination with carvacrol. We evaluated the formation of micronucleus (MN), known as genotoxicity occurrence indicator, to demonstrate the possibility of diphenhydramine-induced genotoxicity. Furthermore, the level of oxidative stress was assumed by cellular glutathione oxidation and lipid peroxidation.

The results showed that high concentrations of diphenhydramine could cause oxidative stress damages by elevating the lipid peroxidation and glutathione oxidation. The frequency of micronucleus increased after diphenhydramine exposure (p < 0.05). Interestingly, carvacrol significantly decreased frequency of micronucleus and lipid peroxidation in lymphocytes exposed to high concentration of diphenhydramine.

  Our results further support the idea that carvacrol has beneficial effects in protecting cells against oxidative stress damages and diphenhydramine-induced genotoxicity.

Development of new medicines with fewer side effects and more efficacy is needed for treatment of depressive and anxiety disorders. The present study was designed to investigate the antidepressant and anti-anxiety effects of Stachys annua L. methanol extract in mice.

The extract was prepared by maceration method and the total phenolic and flavonoid contents were determined by Folin-Ciocalteu and aluminum chloride methods, respectively. Elevated plus-maze (EPM) and open field tests (OFT) were applied to evaluate the anti-anxiety and locomotor activity of animals treated with the intraperitoneal (i.p.) extract (12.5, 25, 50, and100 mg/kg), respectively. Antidepressant activity was evaluated by forced swim test (FST) and tail suspension test (TST).

The total phenolic content of the extract was 54.13±0.01 mg of gallic acid equivalents per gram of dry extract and total flavonoid content was 67.89±0.005 mg of quercetin as equivalents/ g of extract. Intraperitoneal administration of the extract (50 and 100 mg/kg) significantly increased the percentage of time spent and the percentage of arm entries into the open arms of EPM and decreased locomotor activity, compared with the vehicle control group. In addition, the immobility time of animals significantly decreased in both FST and TST with doses of 25, 50, and 100 mg/kg of the extract, compared with the vehicle control group.

The extract of Stachys annua L. might be used as an adjunct therapy in clinical studies for the treatment of depressive and anxiety disorders. However, determination of active ingredients needs further evaluation.

Alzheimer's disease (AD) is characterized by progressive cognitive decline. Oxidative stress plays a central role in the pathogenesis of AD. It has been proposed that administration of antioxidants affect cognitive processes, such as learning and memory. This study investigated the protective effects of vitamin E and Ginkgo biloba extract (as antioxidants) on learning and memory, hippocampal plasticity, and apoptotic marker proteins in a rat model of AD.

The hyroalcoholic extract of Gingko biloba leaves wasprepared using maceration method. Male Wistar rats were randomly divided into six groups: control, sham received intra-hippocampal injection (I.H.P) of vehicle, AD model that received intra-hippocampal injection of the beta-amyloid (Aβ), AD+ vitamin E (200 mg/kg, i.p.), AD+ G. biloba (100 mg/kg/p.o.), and AD+ vitamin E (200 mg/kg, i.p.)+ G. biloba (100 mg/kg/p.o.). At the end of the treatments, the rats were subjected to the passive avoidance learning (PAL) test. The field long wterm potentials (LTP) were recorded in the hippocampal dentate gyrus. Hippocampal expressions of Bax and Bcl-2 (as pro-apoptotic, as anti-apoptotic) proteins were measured by western blot method.

Treatment with G. biloba and vitamin E improved the Aβ-induced memory impairment in the PAL task. Vitamin E and/or G. biloba extract enhanced the population spike amplitude evoked potentials of the LTP components, vitamin E and/or G. biloba extract increased Bcl-2 expression and decreased Bax expression in the hippocampus.

Ginkgo biloba and vitamin E could suppress the expression of apoptosis markers and improved hippocampal LTP impairment and the memory deficit induced by Aβ.

The species of Cymbopogon are generally used for different pharmacological effects. No histopathological study has been conducted on the plant’s toxicity so far. Thus, the acute and repeated toxicity of Cymbopogon essential oil were investigated.

The essential oil from aerial parts of Cymbopogon schoenanthus was administered in mice by gavage in both acute and repeated models. The animals were then divided into control and test groups. In the acute toxicity, 2000 mg/kg C. schoenanthus essential oil was administered in mice. Death rate, toxic symptoms, body weight, and abnormal behaviors were also observed for 14 days. In the repeated toxicity, C. schoenanthus essential oil (10, 100, and 200 mg/kg) was daily administered for a 4-week period. On the 28thday, all animals were sacrificed and their blood and tissue samples were prepared. Moreover, clinical, biochemical, and histopathological changes were compared to the control group.

No mortality was noticed in the acute test; therefore, the oral LD50 value was determined to be greater than 2000 mg/kg in the female mice. In the repeated test, the animals were given C. schoenanthus essential oil, which consequently showed no mortality and toxic symptoms. The repeated administration of C. schoenanthus essential oil had a variation on glucose, urea, Na+, and K+ levels. Moreover, the terminal necropsies revealed low toxic effects on the liver.

The results indicate that the oral acute toxicity of C. schoenanthus essential oil in mice was of a low order with LD50 being more than 2000 mg/kg. Additionally, slight tissue damage to liver was observed when it was administered sub-chronically at the dose of 200 mg/kg.

Interferon-alpha (IFN-α) is a cytokine with various clinical applications, but it may induce depression by decreasing tryptophan level and producing neuroactive metabolites. Since Linum usitatissimum (flaxseed) is a valuable source for amino acids, α-linolenic acid (ALA), and lignans that could prevent inflammation and neurotoxicity, flaxseed effects on IFN-α induced depressant was evaluated.

Flaxseed was applied either by whole ground flaxseeds in mice diet, or flaxseed oil by gavage feeding tube until effective antidepressant effects were observed. Seventy-eight male albino mice 25±3 g were used and divided in 13 groups, IFN-α 16×10 5 IU/kg was injected for 6 days. After the locomotor test, the forced swimming test (FST) was used to measure the immobility time indicating despair behavior, and the sucrose preference test measured anhedonia.

There were only marginal differences in the locomotor activity; however, the immobility time increased by IFN-α (154.5±11.22 s, vs control 121.3±7.14 s; p=0.031), and sucrose preference was 65% indicating depression. The administration of flaxseed 30% or flaxseed oil 25% with IFN-α significantly reduced the immobility time (92.67±11.60 s and 94.17±10.12 s, respectively, vs IFN-α normal diet, p <0.01), sucrose preference also increased that supported the antidepressant effect.

Flaxseed could prevent IFN-α induced depressive-like behavior in mice. Although interpretation from animal to human studies needs careful attention, this study supports the use of flaxseed in the diet as reasonable strategy to prevent depression in high-risk individuals, such as patients treated with IFN-α.

Cisplatin-induced nephrotoxicity accompanies increased oxidative stress, leading eventually to kidney dysfunction. On the other hand, Pistacia vera nuts (pistachio) display multiple pharmacological effects such as antioxidant property. The present study investigated the effects of pistachio hydroalcoholic extract on nephrotoxicity induced by cisplatin in mice.

Pistachios (100 g) were powdered and macerated in 1 L of ethanol (80%) for 72 h Then, dried with rotary evaporator apparatus. Forty male mice were divided into five groups: normal, cisplatin, cisplatin+DMSO, cisplatin+ pistachio hydroalcoholic extract 10, and cisplatin+ pistachio hydroalcoholic extract 100. Nephrotoxicity was induced by intraperitoneal injection of cisplatin (20 mg/kg/day) on the first day of the experiment. Pistachio hydroalcoholic extract (10 and 100 mg/kg/p.o) was administered for four consecutive days. The body weight and kidney function indices such as serum creatinine (Cr) and blood urine nitrogen (BUN) were measured. Also, the renal tissues were assessed for levels of malondialdehyde (MDA), catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx).

Cisplatin reduced animals’ body weight. Also, cisplatin increased levels of Cr, BUN, and MDA, and decreased the activities of SOD, CAT, and GPx. Treatment with pistachio hydroalcoholic extract (100 mg/kg) reduced the levels of serum Cr, BUN, as well as renal MDA. Moreover, administration of 100 mg/kg pistachio hydroalcoholic extract to cisplatin-treated mice increased the body weight as well as CAT, GPx, and SOD activities.

These results imply that pistachio hydroalcoholic extract treatment may diminish cisplatin-induced renal dysfunction through reduction of oxidative stress in the kidney tissue.

Sargassum angustifolium is a brown alga in southwestern coastline of Persian Gulf. Regarding the presence of various bioactive compounds and evidence of antihypertensive effects in other species of Sargassum, we evaluated the effect of S. angustifolium ethanol extract in CdCl2-induced hypertension in Wistar rats.

Alga extract was prepared by maceration method using 70% ethanol and assessed for total phenolics and salt content. CdCl2 (1.5 mg/kg/day) was administered intraperitoneally to the rats for two weeks. Treatment groups received S. angustifolium extract (20, 40 and 80 mg/kg) or nifedipine (10 mg/kg) orally and simultaneously were given CdCl2 for two weeks. Systolic blood pressure (SBP) and heart rate were measured using tail-cuff method. Total antioxidant capacity, urea, creatinine, electrolytesincluding sodium, potassium, calcium and chloride were estimated in blood samples. The weight and histopathology of kidney tissues were also evaluated.

The content of total phenolic as gallic acid equivalent and the salt as NaCl was 67.42 ± 9.5 mg/g and 6.9 g/100 g in dried ethanol extract, respectively. CdCl2 caused significant increase in SBP, kidney/body weight ratio, serum sodium and urea level and decrease in plasma total antioxidant capacity, and also histopathological alterations in kidney tissues. Treatment with S. angustifolium extract at the doses of 40 and 80 mg/kg significantly reversed hypertension and improved kidney weight, urea level and electrolyte changes, and enhanced antioxidant capacity and preventedhistopathological changes of kidney.

Findings of the present study indicated antihypertensive and antioxidant effects of S. angustifolium extract against CdCl2-induced hypertension in rats.

Phellinus belongs to the family of Hymenochaetaceae. In Traditional Chinese Medicine, it has been used as an ingredient for the treatment of different types of cancer, ischemia and skin diseases for thousands of years. The present study was aimed to evaluate and compare the mushroom constituents (total phenolic and flavonoid contents) and antioxidant and cytotoxic effect against cholangiocarcinoma cells.

The samples of Phellinus mushrooms including P. igniarius, P.lineteus and P.nigricans were prepared in two ways: macerated in 95% ethanol and decocted in distilled water. The antioxidant activity of the six  extracts were evaluated using the DPPH, ABTS and FRAP assays. Total phenolics and flavonoids were determined using colorimetric tests. In addition, cytotoxic activities against cholangiocarcinoma cell lines (KKU-100 & KKU213A) were assessed by the SRB assay.

All ethanol extracts of samples showed significantly stronger antioxidant activity compared to aqueous extracts (p <0.05), while the ethanol extracts contained higher total phenolic and flavonoid contents. Phellinus linteus showed the highest antioxidant activity and total phenolic content when compared to P. igniarius and P. nigricans. All samples showed high cytotoxicity against cholangiocarcinoma cell lines, particularly the ethanol extract of P. linteus. The cytotoxicity was correlated to the phytochemical contents and antioxidant activity of each Phellinus mushroom. 

The cytotoxicity and antioxidant activity are in proportion to the phenolic and flavonoid contents. Therefore, the antioxidant capacity of the mushroom extracts may advocate anti-cancer effects.