Panacea seed “Nigella”: A review focusing on regenerative effects for gastric ailments

Nigella sativa (NS) or black cumin is a dark, thin, and crescent-shaped, seeded shrub belonging to the Ranunculaceae family commonly growing on Mediterranean coasts in Saudi Arabia, northern Africa and Asia. They have amazing curative and therapeutic features that make them one of the most popular, safe, non-detrimental, and cytoprotective medicinal plant that can be used for prevention and treatment of many complicated diseases. Originally, N. sativa was used to treat migraines and allergy, and researches have shown its effectiveness in destroying cancer cells as well. The gastro protective effect of NS oil and its constituents has also been reported earlier; however, the complete perception on etiology and pathogenesis of gastric ulcer is not yet clear. Herein, we attempt to unveil some of the potential mechanisms exhibited by NS in preventing problems related to gastric ulcers. Gastric ailments like ulcers and tumors are the most common disorders of the gastro-intestinal tract in the present day life of the industrialized world. Gastric ulcer being a multifaceted problem exhibits complex etiology and is the fourth most common cause of cancer mortality. Drug interactions and toxicity are the main hindrances in chemotherapy. The existing merits and demerits of modern-day drugs make us turn toward the plant kingdom which may provide a valuable resource of novel potent natural compounds for pharmaceuticals or alternately, as dietary supplements. In this context, the revered phytotherapeutic N. sativa comes as a promising savior in today’s times. This review aims to summarize, both the functional and disease-related effects in the area of gastroenterology.     

Nigella sativa L.: Uses in traditional and contemporary medicines – An overview

There are several wild and cultivated plants that offer excellent opportunities for being used as herbal and therapeutic agents. The identification of medicinal properties of plants and their effectiveness in treating diseases are important components in medicinal plant research and this can pave ways for further improvements in traditional drug use. Climatic conditions and phytogeography in Pakistan are ideal for naturally occurring diverse flora and managed cultivation of hundreds of plants of medicinal significance. Nigella sativa commonly known as the black seed is an important medicinal plant that has been widely used as a multipurpose medicinal agent in different countries since old times. The plant is abundantly cultivated in Pakistan for uses as condiment and medicines. It possesses important classes of bioactive compounds among which thymoquinone has attracted significant attention from the scientific community because of its active role in treating a diverse spectrum of diseases. The black seeds are used for reducing adverse effects of arthritis, asthma, inflammation, liver and gastro disorders besides their potential role in diabetes and cancers. The focus of this review is to highlight the medicinal significance of N. sativa in traditional medicine and opportunities for exploitation in contemporary medicine.     

Effects of Nigella sativa L. seed oil on abnormal semen quality in infertile men: A randomized,double-blind,placebo-controlled clinical trial

In recent years, wide utilization of herbal drugs has encouraged scientists to determine their impressive effects on health. Since Nigella sativa L. seed (N. sativa) has many uses including infertility in traditional medicine, the effects of Nigella sativa L. seed oil on abnormal semen quality in infertile men with abnormal semen quality are of interest. This study was conducted on Iranian infertile men with inclusion criteria of abnormal sperm morphology less than 30% or sperm counts below 20 × 10⁶/ml or type A and B motility less than 25% and 50% respectively. The patients in N. sativa oil group (n = 34) received 2.5 ml N. sativa oil and placebo group (n = 34) received 2.5 ml liquid paraffin two times a day orally for 2 months. At baseline and after 2 months, the sperm count, motility and morphology and semen volume, pH and round cells as primary outcomes were determined in both groups. Results showed that sperm count, motility and morphology and semen volume, pH and round cells were improved significantly in N. sativa oil treated group compared with placebo group after 2 months. It is concluded that daily intake of 5 ml N. sativa oil for two months improves abnormal semen quality in infertile men without any adverse effects.     

In-vitro free radical scavenging effect and cytotoxic analysis of Black Cummins and Honey formulation

BackgroundThe antioxidant potential and antiproliferative activity of the extracts of Nigella sativa seeds (Black Cummins) and honey formulations are to be explored.MethodThe gas chromatography-mass spectrum (GC–MS) and Thin Layer Chromatography (TLC) fingerprint of Black Cummins and Honey formulation revealed alkaloid, saponin, volatile oil, flavonoid, glycosides, sugar, and phenolic compound in the extract. GC–MS profiling of the cold extract of Nigella sativa seeds and honey formulation shows peaks for eleven fractions of compounds. Using TLC, the phenolic compounds of Nigella sativa seeds and honey formulations were separated.ResultsThe current study discovers the cytotoxic effect of black Cummins seeds and honey formulation on human ovarian cancer (PA-1) cell line as assessed by MTT assay. PA-1 cells were inhibited with the increasing concentration of Nigella sativa seeds extract and honey formulation.ConclusionThe study validates the importance of the tested extracts in the treatment of cancer.     

Hormetic/Cytotoxic Effects of Nigella sativa Seed Alcoholic and Aqueous Extracts on MCF-7 Breast Cancer Cells Alone or in Combination with Doxorubicin

In this study, we investigate the possible cytotoxic effects of different Nigella sativa seed extracts on human MCF-7 breast cancer cells and screening the effects of a wide range of extracts concentrations and their application as an adjuvant therapy to doxorubicin. The results obtained showed that the cytotoxic solvent dimethyl sulfoxide can be used for permeation assay in concentration range 697.5–0.341 mmol/ml without affecting the viability of MCF-7 cells. N. sativa lipid extract is cytotoxic to MCF-7 cells with LC₅₀ of 2.72 ± 0.232 mg/ml, while its aqueous extract cytotoxicity exhibited when the applied concentration is high as ≈ 50 mg/ml. The results of this study reveal for the first time that low concentrations of aqueous extract of the seed has a hormetic rather than cytotoxic effect. It is also possible to use cell culture medium or bovine serum to dilute the oil extract for the permeation assay. In conclusion, N. sativa aqueous extract should not be used as antitumor compound by its own. The oil is a promising antitumor compound and its cytotoxicity was greatly enhanced with its nanoemulsion formulation. Antitumor activity of doxorubicin was enhanced, as a function of time, when N. sativa extracts were involved as adjunct therapeutic compounds. Adding doxorubicin to the prepared lipid nanoemulsion has a beneficial impact to their bioactivity. These doxorubicin—N. sativa lipid nanoemulsion are promising and potential therapeutic modality.     

Scolicidal Effects of Black Cumin Seed (Nigella sativa) Essential Oil on Hydatid Cysts

Surgery remains the preferred treatment for hydatid cyst (cystic echinococcosis, CE). Various scolicidal agents have been used for inactivation of protoscolices during surgery, but most of them are associated with adverse side effects. The present study aimed to evaluate the in vitro scolicidal effect of Nigella sativa (Ranunculaceae) essential oil and also its active principle, thymoquinone, against protoscolices of hydatid cysts. Protoscolices were aseptically aspirated from sheep livers having hydatid cysts. Various concentrations of the essential oil (0.01-10 mg/ml) and thymoquinone (0.125-1.0 mg/ml) were used for 5 to 60 min. Viability of protoscolices was confirmed by 0.1% eosin staining. Furthermore, the components of the N. sativa essential oil were identified by gas chromatography/mass spectroscopy (GC/MS). Our study revealed that the essential oil of N. sativa at the concentration of 10 mg/ml and its main component, thymoquinone, at the concentration of 1 mg/ml had potent scolicidal activities against protoscolices of Echinococcus granulosus after 10 min exposure. Moreover, thymoquinone (42.4%), p-cymene (14.1%), carvacrol (10.3%), and longifolene (6.1%) were found to be the major components of N. sativa essential oil by GC/MS analysis. The results of this study indicated the potential of N. sativa as a natural source for production of a new scolicidal agent for use in hydatid cyst surgery. However, further studies will be needed to confirm these results by checking the essential oil and its active component in in vivo models.     

The effects of some natural products compared to synthetic products on the metabolic activity,proliferation, viability,migration, and wound healing in sheep tenocytes

BackgroundTendinopathy or tendon injuries can affect many people, causing a huge impact on their movements and maintaining standing posture. Treatment options include physiotherapy, anti-inflammatory drugs, and alternative medicine. The use of physiotherapy or anti-inflammatory drugs may cause some side effects like pain and liver failure, respectively, therefore, alternative medicine will be a better choice.MethodTenocytes were isolated from sheep Achilles tendon and used in Alamar blue assay to assess the metabolic activity, proliferation, and viability of tenocytes over 24 hrs. and 48 hrs., using natural and synthetic products [i.e., olive oil, oleic acid, corn oil, Inula viscosa oil, Inula viscosa extract, Nigella sativa oil, naproxen sodium, and paracetamol and LED photobiomodulation]. Furthermore, tenocytes viability was assessed by FDA/PI stain. For migration and healing of a wound, the scratch assay was used.ResultsAlamar blue assay over 24 hrs. showed that Nigella sativa oil increased the metabolic activity, proliferation, and viability of tenocytes significantly, while Alamar blue over 48 hrs. showed that oleic acid, LED, and their combination increased these parameters for tenocytes significantly. Olive oil increased the viability of tenocytes significantly using FDA/PI stains. Scratch assay revealed that Inula viscosa oil, Inula viscosa extract, and paracetamol increased tenocyte migration and healing significantly.ConclusionNigella sativa oil, olive oil, oleic acid, Inula viscosa oil, and Inula viscosa extract may be used as an alternative therapy for tendinopathy with less side effects.     

Anti-inflammatuar and anti-oxidative effects of Nigella sativa L.: 18FDG-PET imaging of inflammation

Inflammation has an important role in many diseases such as cystic fibrosis, allergies and cancer. The free radicals produced during inflammation, can induce gene mutations and posttranslational modifications of cancer related proteins. Nigella sativa L. (N. sativa) is herbaceous plant and commonly used as a natural food. It has many pharmacological effects including antibacterial, antifungal, antitumor, analgesic, antipyretic activity. The aim of this study was to investigate the anti-inflammatuar and anti-oxidant activity of N. sativa in acute inflammation. Thus we used the experimental lipopolysaccharides (LPS)-induced model. Intraperitoneal LPS 1 mg/kg was administered to groups. N. sativa (500 mg/kg) and essential oil (5 ml/kg) were given orally to treatment groups, after 24-h of intraperitoneal LPS-injection. To determine the lung inflammation, ¹⁸F-fluoro-deoxy-d-glucose (0.8 ml/kg) was administrated under the anesthesia before the 1 h of PET-scanning. After the FDG-PET, samples were collected. Lung and liver ¹⁸F-FDG-uptake was calculated. Serum AST, ALT, LDH and hcCRP levels were determined and liver, lung and erythrocyte SOD, MDA and CAT levels were measured. Liver and lung NO and DNA fragmentation levels were determined. MDA levels were decreased in treated inflammation groups whereas increased in untreated inflammation group. SOD and CAT activities in untreated inflammation group were significantly lower. According to the control group, increased AST and ALT levels were found in untreated inflammation group. ¹⁸F-FDG uptake of inflammation groups were increased when compare the control group. We found increased ¹⁸F-FDG uptake, DNA fragmentation and NO levels in LPS-induced inflammation groups. We conclude that, in LPS-induced inflammation, N. sativa have therapeutic and anti-oxidant effects.     

Potential influence of Nagella sativa (Black cumin) in reinforcing immune system: A hope to decelerate the COVID-19 pandemic

The world is witnessing a difficult time. The race of developing a new coronavirus (COVID-19) vaccine is becoming more urgent. Many preliminary studies on the pathophysiology of COVID-19 patients have provided some clues to treat this pandemic. However, no suitable treatment has found yet. Various symptoms of patients infected with COVID-19 indicated the importance of immune regulation in the human body. Severe cases admitted to the intensive care unit showed high level of pro-inflammatory cytokines which enhanced the disease severity. Acute Respiratory Distress Syndrome (ARDS) in COVID-19 patients is another critical factor of disease severity and mortality. So, Immune modulation is the only way of regulating immune system. Nigella sativa has been used for medicinal purposes for centuries. The components of this plant are known for its intense immune-regulatory, anti-inflammatory, and antioxidant benefits in obstructive respiratory disorders. A molecular docking study also gave evidences that N. sativa decelerates COVID-19 and might give the same or better results than the FDA approved drugs. The aim of this review was to investigate the possible immune-regulatory effects of N. sativa on COVID-19 pandemic. Our review found N. sativa's Thymoquinone, Nigellidine, and α-hederin can be a potential influencer in reinforcing the immune response on molecular grounds.     

A comprehensive perspective of traditional Arabic or Islamic medicinal plants as an adjuvant therapy against COVID-19

COVID-19 is a pulmonary disease caused by SARS-CoV-2. More than 200 million individuals are infected by this globally. Pyrexia, coughing, shortness of breath, headaches, diarrhoea, sore throats, and body aches are among the typical symptoms of COVID-19. The virus enters into the host body by interacting with the ACE2 receptor. Despite many SARS-CoV-2 vaccines manufactured by distinct strategies but any evidence-based particular medication to combat COVID-19 is not available yet. However, further research is required to determine the safety and effectiveness profile of the present therapeutic approaches. In this study, we provide a summary of Traditional Arabic or Islamic medicinal (TAIM) plants' historical use and their present role as adjuvant therapy for COVID-19. Herein, six medicinal plants Aloe barbadensis Miller, Olea europaea, Trigonella foenum-graecum, Nigella sativa, Cassia angustifolia, and Ficus carica have been studied based upon their pharmacological activities against viral infections. These plants include phytochemicals that have antiviral, immunomodulatory, antiasthmatic, antipyretic, and antitussive properties. These bioactive substances could be employed to control symptoms and enhance the development of a possible COVID-19 medicinal synthesis. To determine whether or if these TAIMs may be used as adjuvant therapy and are appropriate, a detailed evaluation is advised.     

Anti-Inflammatory Activity of S. Marianum and N. Sativa Extracts on Macrophages

Background:Nigella sativa (N. sativa) and Silybum marianum (S. marianum) are used to regulate macrophage polarization in lipopolysaccharide-induced RAW 264.7 cells and thioglycollate-elicited peritoneal inflammation.Methods:Cytotoxicity assays and acute toxicity tests were performed to investigate the safe dose and toxicity of the prepared extracts. Also, nitric oxide production was determined by Griess assay on RAW264.7 and peritoneal macrophage supernatants. After RNA extraction from macrophages, real-time PCR was performed to measure the relative gene expression of tumor necrosis factor (TNF)-α, interleukin (IL)-6, transforming growth factor (TGF)-β, and IL-10. Finally, regulatory T cells (Treg cells) were counted by flow cytometry.Results:S. marianum methanolic extract (SME), N. sativa ethanolic extract (NEE), and their mixture (SME+NEE) decreased NO levels significantly in RAW264.7 and peritoneal murine macrophages. N. sativa ethanolic extract significantly increased IL-10 gene expression and significantly decreased IL-6 and TNF-α expression in RAW264.7 cells. In mixture-treated peritoneal macrophages, IL-10 and TGF-β expression were significantly increased, while IL-6 and TNF-α were significantly decreased. Also, the percentage of Treg cells was significantly greater in the mixture-treated cells than in controls.Conclusion:These results suggest that an SME and NEE mixture has anti-inflammatory and immunomodulatory activities and may be useful in the treatment of diseases of immunopathologic origin characterized by macrophage hyperactivation.Key Words: Cytokine, Inflammation, Nigella sativa, Nitric oxide, Silybum marianum     

Induction of apoptosis in HeLa cells by chloroform fraction of seed extracts of Nigella sativa

Background  

Cancer remains one of the most dreaded diseases causing an astonishingly high death rate, second only to cardiac arrest. The fact that conventional and newly emerging treatment procedures like chemotherapy, catalytic therapy, photodynamic therapy and radiotherapy have not succeeded in reverting the outcome of the disease to any drastic extent, has made researchers investigate alternative treatment options. The extensive repertoire of traditional medicinal knowledge systems from various parts of the world are being re-investigated for their healing properties. This study progresses in the direction of identifying component(s) from Nigella sativa with anti cancer acitivity. In the present study we investigated the efficacy of Organic extracts of Nigella sativa seed powder for its clonogenic inhibition and induction of apoptosis in HeLa cancer cell.     

Solvent based optimization for extraction and stability of thymoquinone from <Emphasis Type="Italic">Nigella sativa</Emphasis> Linn. and its quantification using RP-HPLC

The Nigella sativa pharmacological properties are mainly ascribed to its volatile oil, of which thymoquinone is an important bioactive component. Surprisingly, till date, no standard formulation or thymoquinone rich N. sativa extract is under clinical use probably due to its poor extraction and lesser stability in the already used solvents. In the present investigation solubility, extraction, percent composition and total antioxidant activity from the seeds of N. sativa was explored using five solvents. An HPLC method was standardized in an isocratic system (C-18 column, flow rate of 1.0 ml/min, mobile phase—water:methanol: 30:70, detection wavelength—254 nm, retention time—8.77 min) for quantification of thymoquinone. To further confirm the presence of thymoquinone in the respective extracts absorbance spectra analysis has been carried out and compared with pure thymoquinone. Additionally total antioxidant activity of Nigella sativa extracts has been evaluated using ascorbic acid as standard. Our results showed maximum percentage yield in aqueous extract while methanol having the least yield and the ethanol, benzene and hexane extracts exhibited moderate yields. A linear standard calibration curve of thymoquinone showed R² as 0.999 and % RSD as 7.166. The HPLC analysis revealed maximum percentage composition of thymoquinone in the benzene extract, whereas in the hexane and methanol extracts the content was less. Aqueous and ethanol extracts displayed insignificant thymoquinone content. Absorbance spectra analysis confirms the presence of thymoquinone peak in the benzene, hexane and methanol extracts while aqueous and ethanol extracts showed minimal absorbance. Maximum total antioxidant activity was observed in the aqueous extract while minimum was observed in the methanolic extract. Weak positive (+?0.3676) correlation was established between percent composition of thymoquinone and antioxidant activity among different extracts indicating that thymoquinone may not be the only factor for antioxidant activity, but other phytochemicals might also contribute. However, we for the first time demonstrated that the benzene extract of N. sativa has better solubility and percent composition of thymoquinone as compared to other solvents. It can be concluded that the solubility, differential composition of bioactive components among these extracts may have diverse effects on the total antiradical activity. Thus, our study provides insights on optimization and standardization of bioactive rich formulation of N. sativa.     

A review of medicinal plant of Middle East and North Africa (MENA) region as source in tuberculosis drug discovery

Tuberculosis (TB) is a disease that affects one-third of the world’s population. Although currently available TB drugs have many side effects, such as nausea, headache and gastrointestinal discomfort, no new anti-TB drugs have been produced in the past 30 years. Therefore, the discovery of a new anti-TB agent with minimal or no side effects is urgently needed. Many previous works have reported the effects of medicinal plants against Mycobacterium tuberculosis (MTB). However, none have focused on medicinal plants from the Middle Eastern and North African (MENA) region. This review highlights the effects of medicinal plants from the MENA region on TB. Medicinal plants from the MENA region have been successfully used as traditional medicine and first aid against TB related problems. A total of 184 plants species representing 73 families were studied. Amongst these species, 93 species contained more active compounds with strong anti-MTB activity (crude extracts and/or bioactive compounds with activities of 0–100 µg/ml). The extract of Inula helenium, Khaya senegalensis, Premna odorata and Rosmarinus officinalis presented the strongest anti-MTB activity. In addition, Boswellia papyrifera (Del) Hochst olibanum, Eucalyptus camaldulensis Dehnh leaves (river red gum), Nigella sativa (black cumin) seeds and genus Cymbopogon exhibited anti-TB activity. The most potent bioactive compounds included alantolactone, octyl acetate, 1,8-cineole, thymoquinone, piperitone, α- verbenol, citral b and α-pinene. These compounds affect the permeability of microbial plasma membranes, thus kill the mycobacterium spp. As a conclusion, plant species collected from the MENA region are potential sources of novel drugs against TB.     

Pharmacological intervention of biosynthesized Nigella sativa silver nanoparticles against hexavalent chromium induced toxicity in male albino mice

Hexavalent chromium, toxic heavy metal, among the top-rated environmental contaminants, is declared a potent endocrine disruptor in humans and animals. The present study was planned to find harmful effects on the reproductive system caused by Cr (VI) and the ameliorative effect of Nigella sativa and Nigella sativa-mediated AgNP on male mice (Mus musculus). In the present study, known infertility medicine, clomiphene citrate is also used as a positive control. The main objective of the present study was to assess the ameliorative potential of oral administration of a dose of 50 mg/kg BW clomiphene citrate (control), AgNP via chemical synthesis, Nigella sativa seed extract, and Nigella sativa-mediated AgNP against the Cr (VI) at the dose of 1.5 mg/kg BW from K₂Cr₂O₇ orally induced toxicity over eight weeks on the reproductive performance of male albino mice. Nigella sativa mediated AgNPs were characterized by UV, SEM, FTIR, and XRD. The histological analysis, smear study, antioxidant capacity test, and hormone analysis were conducted by blood samples of albino mice. Cr exposed groups showed a significant decrease in sperm head breadth (5.29 ± 0.54 µ) and length (19.54 ± 1.18 µ), middle piece length, tail length, LH (1.65 ± 0.15 ng/mL), testosterone (2.63 ± 0.29 ng/mL), SOD (61.40 ± 2.48 mmol/mL), CAT (87.40 ± 6.01 mmol/mL), GSH (1.54 ± 0.09 µmol/mL), and no of spermatogonia (1.22 ± 0.25), and spermatocytes (2.33 ± 0.943). However, FSH level (160.00 ± 4.98 ng/mL), seminiferous tubule CSA (1094.69 ± 49.76 mm²), size of spermatogonia (41.30 ± 1.24 µ), and spermatocytes (26.07 ± 1.34 µ) were significantly increased. Administration of Nigella sativa and Nigella sativa-mediated AgNPs reduced the toxicity.     

Effects of Nigella sativa oil on ovarian volume,oxidant systems,XIAP and NF-kB expression in an experimental model of diabetes

ABSTRACT

We investigated the effects of Nigella sativa oil on ovary volume, nuclear factor-kappaB (NF-κB), X-linked inhibitor of apoptosis protein (XIAP) expression, and serum malondialdehyde (MDA), superoxide dismutase (SOD), total antioxidant status (TAS) and total oxidant status (TOS) levels in diabetic rats. We divided 21 adult female rats into three groups: controls, diabetics and diabetics + N. sativa oil. The diabetics + N. sativa oil group was given 0.2 mg/kg/day N. sativa oil 6 days/week for 4 weeks. NF-κB and XIAP expression was assessed in ovarian sections using immunohistochemistry. The right and left ovary volumes were calculated using stereology. We also measured serum MDA, SOD, TAS and TOS levels. We found that N. sativa oil reduced hyperglycemia, but not to control levels. N. sativa oil also exhibited antioxidant properties as demonstrated by reduced serum TOS and MDA levels, and increased SOD and TAS levels compared to controls. We found no significant difference in total ovarian volume, XIAP or NF-κB expression among the groups, which may be due to the short study period. Our findings suggest that N. sativa oil may be useful for reducing blood glucose levels and elevated oxidant activity in diabetic patients.     

Acute and chronic toxicity of Nigella sativa fixed oil

We investigated the toxicity of the fixed oil of Nigella sativa L seeds in mice and rats through determination of LD50 values and examination of possible biochemical, hematological and histopathological changes. The acute toxicity of Nigella sativa fixed oil was investigated in mice. LD50 values, obtained by single doses, orally and intraperitoneally administered in mice, were 28.8 ml/kg body wt. p.o. [26.2-31.6] and 2.06 ml/kg body wt. i.p. [1.86-2.26], respectively. Chronic toxicity was studied in rats treated daily with an oral dose of 2 ml/kg body wt. for 12 weeks. Changes in key hepatic enzymes levels, including aspartate-aminotransferase, alanine-aminotranferase, and gamma-glutamyltransferase and histopathological modifications (heart, liver, kidneys and pancreas) were not observed in rats treated with Nigella sativa after 12 weeks of treatment. The serum cholesterol, triglyceride and glucose levels and the count of leukocytes and platelets decreased significantly, compared to control values, while hematocrit and hemoglobin levels increased significantly. A slowing of body weight gain was also observed in Nigella sativa treated rats, as compared to control animals. The low toxicity of Nigella sativa fixed oil, evidenced by high LD50 values, key hepatic enzyme stability and organ integrity, suggests a wide margin of safety for therapeutic doses of Nigella sativa fixed oil, but the changes in hemoglobin metabolism and the fall in leukocyte and platelet count must be taken into consideration.     

Blockade of Nitric Oxide Overproduction and Oxidative Stress by <Emphasis Type="Italic">Nigella sativa</Emphasis> Oil Attenuates Morphine-Induced Tolerance and Dependence in Mice

The effects of Nigella sativa oil on morphine-induced tolerance and dependence in mice and possible mechanism(s) of these effects were investigated, for the first time, in this study. Repeated administration of Nigella sativa oil (4 ml/kg, p.o.) along with morphine (5 mg/kg, s.c.) attenuated the development of tolerance, as measured by the hot plate test, and dependence, as assessed by naloxone (5 mg/kg, i.p.)-precipitated withdrawal manifestations. Concomitantly, nitric oxide overproduction and increase in brain malondialdehyde level induced by repeated administration of morphine to mice or by administration of naloxone to morphine-dependent mice were inhibited by co-administration of the oil. Also, the decrease in brain intracellular reduced glutathione level and glutathione peroxidase activity induced by both treatments were inhibited by co-administration of the oil. The increase in brain glutamate level induced by both treatments was not inhibited by concurrent administration of the oil. The inhibitory effect of the oil on morphine-induced tolerance and dependence and on naloxone-induced biochemical alterations in morphine-dependent mice was enhanced by concurrent i.p. administration of the NMDA receptor antagonist, dizocilpine (0.25 mg/kg). Similarly, concurrent i.p. administration of the NO synthase inhibitors; L-N (G)-nitroarginine methyl ester (10 mg/kg), aminoguanidine (20 mg/kg) and 7-nitroindazole (25 mg/kg) or the antioxidant, N-acetylcysteine (50 mg/kg) enhanced this inhibitory effect of the oil. On the other hand, this effect was antagonized by concurrent i.p. administration of the nitric oxide precursor, L-arginine (300 mg/kg). These results provide evidence that Nigella sativa oil, through inhibition of morphine-induced NO overproduction and oxidative stress, appears to have a therapeutic potential in opioid tolerance and dependence.     

In silico analysis of quranic and prophetic medicinals plants for the treatment of infectious viral diseases including corona virus

Coronavirus disease (COVID-19) is an infection of the respiratory system caused by single standard RNA viruses named as Severe Acute Respiratory Syndrome 2 (SARS-CoV-2). The disease appeared as a serious problem and the leading cause of death in human beings throughout the world. The main source of different phytochemicals are plants, which helps in the development of new drugs against various ailments. Islam is comprehensive religion and a complete code of life for Muslims. The teaching of Islam, according to the Holy Quran and Hadith are universal for the benefit of humanity. Islam believes that every ailment is from God and who made the disease definitely made its medication. There is a complete guideline with regard to taking measures against infectious diseases such as quarantine and seeking medicinal treatment. The research objective is to gather the knowledge of medicinal plants described in the Holy Quran or utilized by the Prophet (SAW) for the treatment of different ailments or advised to use them to boost immunity and strengthen the body. Scientists across the globe have found these plants beneficial for many diseases and have antiviral potential. In present study, the six plant species including Olea europaea, Nigella sativa, Allium Sativum, Allium cepa, Zingiber officinale and Cassia senna were selected which contain phytochemicals like Calcium Elenolate, Thymoquinone, S-Allylcysteine, Dipropyl Disulfide, Sesquiterpene, Monoterpene, Pelargonidin 3-Galactoside ion and Kaempferol. The phytochemicals monoterpene (from Zingiber officinale) shows best interaction with target proteins RdRP, 3CLPro, ACE2. Calcium Elonate (from olive) bonds with 3CLPro, ACE2 and Kemoferol and Pelargomidine (from Senna Makki) bonds with RdRP, ACE2. The ligands show a unique set of intersections i.e. hydrogen bonding, and alkyl interaction. These medicinal plants can be utilized immediately for the treatment of COVID-19 as their safety is already established. This treatment can enhance recovery when combined with other treatments. Furthermore, the screening of bioactive compounds or phytochemicals found in these plants can be utilized to design new therapeutic drug to treat COVID-19 pandemic.