Evidence-based anti-viral and immunomodulatory potential of Black cumin (Nigella sativa L) in COVID-19 / Potencial antivírico e inmunomodulador en COVID-19 del comino negro (Nigella sativa L) basado en la evidencia

Currently, the whole world is facing a life-threatening novel coronavirus 2019 (COVID-19) pandemic. Natural products are well-known for their potential role against viral disease, and some anti-viral agents have been developed to combat these diseases. Herein, the authors investigated the possible effects of this Holy plant Nigella sativa L. (NS), against coronavirus, using evidence-based and mechanistic approaches to conclude the immune-boosting and alleviation of respiratory systemeffects of NS. The pharmacological studies established a prominent role in treating various respiratory, immune systems, cardiovascular, skin, and gastrointestinal disorders. Literature supported the significant anti-viral role and showed an inhibitory role for NS against MHV-A59 CoV (mouse-hepatitis virus­A59) infected Hela, i.e., HeLaCEACAM1a (HeLa-epithelial carcinoembryonic antigen-related cell adhesion molecule 1a) cell. NS is a safe herbal product or dietary supplement and could be an effective and affordable community adjuvant treatment for coronavirus in the current scenario.

Actualmente, el mundo entero se enfrenta a una pandemia del nuevo coronavirus 2019 (COVID-19) que amenaza la vida. Los productos naturales son bien conocidos por su papel potencial contra las enfermedades virales, y se han desarrollado algunos agentes antivirales para combatir estas enfermedades. En este documento, los autores investigaron los posibles efectos de esta planta sagrada Nigella sativa L. (NS), contra el coronavirus, utilizando enfoques mecanicistas y basados en la evidencia para concluir el refuerzo inmunológico y el alivio de los efectos del SN en el sistema respiratorio. Los estudios farmacológicos establecieron un papel destacado en el tratamiento de diversos trastornos respiratorios, del sistema inmunológico, cardiovasculares, cutáneos y gastrointestinales. La literatura apoyó el importante papel antivírico y mostró un papel inhibidor de NS contra células Hela infectadas con MHV-A59 CoV (virus de la hepatitis de ratón-A59), es decir, HeLaCEACAM1a (molécula de adhesión celular 1a relacionada con el antígeno carcinoembrionario epitelial de HeLa). NS es un producto a base de hierbas o un suplemento dietético seguro y podría ser un tratamiento adyuvante comunitario eficaz y asequible para el coronavirus en el escenario actual.

In-vitro evaluation of Nigella sativa and Punica granatum effect on protoscolices of hydatid cysts / Avaliação in vitro do efeito de Nigella sativa e Punica granatum em protoescólices de cistos hidáticos

Abstract Cystic echinococcosis (CE) are commonly found in the liver and lungs of affected hosts. The treatment approach is usually surgical, or giving drugs in conjunction before surgery to kill protoscolices, to avoid anaphylactic shock from leakage of hydatid fluid into the peritoneum and to decrease opportunities for recurrences. The present study was to evaluate the in vitro scolicidal efficacy of hydroalcoholic extract of Punica granatum peel and Nigella sativa, on the protoscolices of CE that collected from the lungs of infected camels. Different concentrations of extracts with different exposure times were used and a viability assay was applied to measure the scolicidal effect. N. sativa showed its highest scolicidal efficacy at 100 mg/mL and 10 mg/mL concentrations after 30 and 60 min. P. granatum peel extract showed its maximum scolicidal efficacy at 100 mg/mL concentration after 120 min. All experiments of the current study revealed that the extracts of both N. sativa and P. granatum had a scolicidal effects on the protoscolices of camel hydatid cysts. It could be concluded that N. sativa extract is more potent than P. granatum peel extract regarding scolicidal effect, but the efficacies of both extracts were of moderate significant correlation to exposure time and concentrations.

Resumo Os cistos hidáticos (equinococose cística, CE) são comumente encontrados no fígado e nos pulmões dos hospedeiros afetados. A abordagem do tratamento geralmente é cirúrgica, e algumas drogas são administradas em conjunto antes da cirurgia para matar protoscólices e evitar choque anafilático devido ao vazamento de fluido hidático no peritônio e diminuir as oportunidades de recorrência. O presente estudo foi avaliar a eficácia in-vitro do extrato hidroalcoólico de casca de Punica granatum e Nigella sativa, sobre os protoescólices de cistos hidáticos, que foram coletados dos pulmões de camelos infectados. Concentrações dos extratos com diferentes tempos de exposição foram utilizados e um ensaio de viabilidade foi aplicado para medir o efeito escolicida. A N. sativa apresentou sua maior eficácia escolicida nas concentrações de 100 mg/mL e 10 mg/mL após 30 e 60 min. O extrato de casca de P. granatum mostrou sua máxima eficácia escolicida na concentração de 100 mg/mL após 120 min. Todos os experimentos do presente estudo revelaram que os extratos de N. sativa e P. granatum tiveram efeito escolicida dependente da dose e do tempo nos protoescólices dos cistos hidáticos de camelo. Pode-se concluir que o extrato de N. sativa é mais potente que o extrato de casca de P. granatum em relação ao efeito escolicida, mas a eficácia de ambos os extratos foi de correlação significativa moderada com o tempo de exposição e as concentrações.

Synergistic effect of honey and Nigella sativa on wound healing in rats

Abstract Purpose: To investigate the therapeutic potential of honey, Nigella sativa (N. sativa) and their combination in rat model of excisional wound healing. Methods: A circular excision wound was established in the back region of 50 Wistar rats. Subsequently, they were divided into 5 groups and daily topical administration of lanolin in the control group, honey in the honey group, cold-pressed N. sativa seed oil in the N. sativa groups, mix of 1:1 ratio of honey and N. sativa seed oil in the mix group, and phenytoin cream in the phenytoin group were used. Then, wound surface areas were evaluated using digital camera immediately after the injury and at post excision days 5, 10, 15 and 20. Results: Significant reduction in wound surface area was observed within and between the groups (P < 0.001). In the post excision days 5, 10, 15 and 20 the wound surface areas in the mix group were significantly lower than the other groups followed by the phenytoin, honey, N. sativa, and control groups. Conclusion: The wound healing may be improved and accelerated by using topical solutions of honey, N. sativa seed oil and especially their mixture.

Mechanisms of the antihypertensive effects of Nigella sativa oil in L-NAME-induced hypertensive rats

OBJECTIVES: This study was conducted to determine whether the blood pressure-lowering effect of Nigella sativa might be mediated by its effects on nitric oxide, angiotensin-converting enzyme, heme oxygenase and oxidative stress markers. METHODS: Twenty-four adult male Sprague-Dawley rats were divided equally into 4 groups. One group served as the control (group 1), whereas the other three groups (groups 2-4) were administered L-NAME (25 mg/kg, intraperitoneally). Groups 3 and 4 were given oral nicardipine daily at a dose of 3 mg/kg and Nigella sativa oil at a dose of 2.5 mg/kg for 8 weeks, respectively, concomitantly with L-NAME administration. RESULTS: Nigella sativa oil prevented the increase in systolic blood pressure in the L-NAME-treated rats. The blood pressure reduction was associated with a reduction in cardiac lipid peroxidation product, NADPH oxidase, angiotensin-converting enzyme activity and plasma nitric oxide, as well as with an increase in heme oxygenase-1 activity in the heart. The effects of Nigella sativa on blood pressure, lipid peroxidation product, nicotinamide adenine dinucleotide phosphate oxidase and angiotensin-converting enzyme were similar to those of nicardipine. In contrast, L-NAME had opposite effects on lipid peroxidation, angiotensin-converting enzyme and NO. CONCLUSION: The antihypertensive effect of Nigella sativa oil appears to be mediated by a reduction in cardiac oxidative stress and angiotensin-converting enzyme activity, an increase in cardiac heme oxygenase-1 activity and a prevention of plasma nitric oxide loss. Thus, Nigella sativa oil might be beneficial for controlling hypertension.

Study on the effect of black cumin (Nigella sativa Linn.) on experimental renal ischemia-reperfusion injury in rats

PURPOSE: To evaluate the effect of Black cumin (Nigella sativa Linn.) pre-treatment on renal ischemia/reperfusion (I/R) induced injury in the rats.METHODS: A total of 40 male Wistar rats were randomly allocated into five equal groups including Sham, I/R model and three I/R+ Black cumin (0.5, 1 and 2%)-treated groups. I/R groups' kidneys were subjected to 60 min of global ischemia at 37°C followed by 24 h of reperfusion. At the end of reperfusion period, the rats were euthanized. Superoxide dismutase, catalase and glutathione peroxidase activities as well as reduced glutathione and renal malondialdehyde contents were determined in renal tissues. Kidney function tests and histopathological examination were also performed.RESULTS: High serum creatinine, blood urea nitrogen and uric acid as well as malondialhehyde (MDA) levels, and low antioxidant enzyme activities were observed in I/R rats compared to the sham rats. Pre-treatment with Black cumin for three weeks prior to IR operation improved renal function and reduced I/R induced renal inflammation and oxidative injury. These biochemical observations were supported by histopathological test of kidney sections.CONCLUSION:Black cumin significantly prevented renal ischemia/reperfusion induced functional and histological injuries.

Therapeutic efficacy of Nigella sativa Linn. seed extract against CCl4 induced hepatic injury in wistar rats.

Carbon tetrachloride (CCl4) intake damages liver. We evaluated therapeutic potential of aqueous extract of Nigella sativa seeds against CCl4 induced liver damage in rats. The hepatic damage induced by CCl4 @ 1.5 mL/kg, ip was evidenced by a significant increase in the serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin, protein and urea lipid peroxidation (LPO) as well as reduction in hepatic antioxidant system e.g. reduced glutathione. Hepatic total protein and glucose-6-phosphatase activity were found decreased. Histological studies substantiated the above biochemical findings. However, after 48 h of administration of aqueous extract of N. sativa seeds (250, 500 and 750 mg/kg, po) it not only detoxified the toxicity but also reversed LPO, GSH, AST, ALT and serum protein changes at all the three doses. Both higher doses of extract were found effective in monitoring urea, albumin, total protein and G-6-Pase activity. However, on the basis of percent protection highest dose i.e., 750 mg/kg proved better. The result suggests that the aqueous extract of N. sativa seeds can be used as a hepatoprotective agent.

Influence of combined administration of turmeric and black seed on selected biochemical parameters of diabetic rats

The objective of the present study was to investigate the effect of Turmeric [Curcuma Longa] and Black cumin seed [Nigella Sativa] mixture on selected biochemical parameters of streptozotocin [STZ] induced diabetic rats. Therefore, twenty one healthy adult albino rats divided into three groups [7 rats in each]. Rats of first and second groups were non diabetic and diabetic respectively. Rats of the third group were diabetic and received a mixture of Turmeric [0.5 g/kg b .wt.] and Black cumin seed [1 g/kg b.wt.] orally by intragastric intubations once a day for six weeks. The changes in blood glucose level, body weight and water and food intake were measured. In addition, selected biochemical parameters were also determined. The present study revealed that, dietary supplementation of plant mixture of Turmeric and Black cumin seed to diabetic rats significantly [P<0.05] reduced the blood glucose level as well as water and food intake accompanied by an increase in body weight gain when compared with untreated diabetic rats. Proteins were not affected whereas liver and kidney functions were disrupted in STZ-diabetic rats and restored whenever treated by medicinal plants mixture. Hypercholesterolemia and hyperlipidemia observed in STZ-diabetic rats were attenuated by administration of examined medicinal plants combination. Conclusively, dietary supplementation of Turmeric and Black cumin seed mixture reduced blood glucose level and ameliorated the hypercholesterolemia and hyperlipidemia in STZ induced diabetic rats

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.

effect of Nigella sativa on the thymus of young and adult rats: Histological, immunohistochemical, and morphometric study

The thymic microenvironment plays a central role in T-cell differentiation. Involution of the thymus begins relatively early in life, resulting in decreased immunity. Nigella sativa is known for its immunopotentiating effects. The aim of the study was to elucidate the effect of N. sativa on the structure of the thymus in young and mature adult rats. Twenty-eight male Wistar albino rats were divided into two groups: group I and group II. Group I was further divided into subgroup Ia and subgroup Ib. Subgroup Ia included seven 1-month-old young rats weighing 50-60 g that received plain water by gavage for 15 days. Subgroup Ib included seven young rats that received 2 ml/kg body weight of 1% petroleum ether extract of N. sativa by gavage for 15 days. Group II was further divided into subgroup IIa and subgroup IIb. Subgroup IIa included seven mature 12-month-old adult rats weighing 600-650 g that received plain water by gavage for 15 days. Subgroup IIb included seven mature adult rats that received 2 ml/kg body weight of 1% petroleum ether extract of N. sativa by gavage for 15 days. Thymi from different subgroups were processed for histological, immunohistochemical, and morphometric studies. In subgroup Ib, the thymus of N. sativa-treated rats revealed a significant increase in the number of CD3-positive cells in the cortex. Some CD3-positive cells were seen in the medulla. In subgroup IIa, signs of thymic involution in the form of expansion of perivascular spaces containing adipocytes and stromal cells with a significant decrease in the number of CD3-positive cells were noticed. In addition, CI cells non reticular thymulin secreting cells along the capillaries were detected. In N. sativa-treated adult rats [subgroup IIb], restoration of the normal stroma and parenchyma occurred. Moreover, a significant increase in the number of CD3-positive cells in the cortex and medulla with an increase in the secretory activity of reticuloepithelial cells was noticed. Oral administration of the petroleum ether extract of N. sativa for 15 days to young and mature adult rats results in enhanced proliferation of thymocytes and increased activity of reticuloepithelial cells

The effect of Nigella sativa extract on tracheal responsiveness and lung inflammation in ovalbumin-sensitized guinea pigs

OBJECTIVE: To examine the preventive effect of a hydro-ethanolic extract of Nigella sativa on the tracheal responsiveness and white blood cell count in the lung lavage fluid of sensitized guinea pigs. METHODS: Three groups of guinea pigs sensitized to intraperitoneally injected and inhaled ovalbumin were given drinking water alone (group S), drinking water containing a low concentration of N. sativa extract (group S+LNS) or drinking water containing a high concentration of N. sativa extract (group S+HNS). The tracheal responses of control animals (group C) and the three groups of sensitized guinea pigs (n = 7 for all groups) to methacholine were measured by the assessment of the tracheal smooth muscle response to increasing concentrations of methacholine, and the effective concentration causing 50 percent of the maximum response (EC50) was determined. Tracheal responses to 0.1 percent ovalbumin and white blood cell counts in the lung lavage fluid were also examined. RESULTS: The tracheal response of the group S guinea pigs to both methacholine and ovalbumin was significantly higher than the response of the controls (p<0.01 for both cases). The tracheal responses of the S+LNS and S+HNS groups to both methacholine and ovalbumin were significantly decreased compared to those of the S group (p<0.05 to p<0.01). The total white blood cell and eosinophil counts in the lung lavage fluid of group S were significantly higher than those of group C (p<0.01). The white blood cell counts in both treated groups showed significant improvements (p<0.01 for both cases). CONCLUSIONS: These results demonstrate the preventive effect of the N. sativa extract on the tracheal response and lung inflammation in sensitized guinea pigs.

The effect of antioxidant properties of aqueous garlic extract and Nigella sativa as anti-schistosomiasis agents in mice / O efeito das propriedades antioxidantes do extrato aquoso do alho e da Nigella sativa como agentes anti-esquistossômicos no camundongo

The aim of this study was to assess the antioxidant and anti-schistosomal activities of the garlic extract (AGE) and Nigella sativa oil (NSO) on normal and Schistosoma mansoni-infected mice. AGE (125 mg kg-1, i.p.) and NSO (0.2 mg kg-1, i.p.) were administrated separately or in combination for successive 28 days, starting from the 1st day post infection (pi). All mice were sacrificed at weeks 7 pi. Hematological and biochemical parameters including liver and kidney functions were measured to assess the progress of anemia, and the possibility of the tissue damage. Serum total protein level, albumin, globulin and cholesterol were also determined. Malondialdehyde (MDA) and glutathione (GSH) levels were determined in the liver tissues as biomarkers for oxidative and reducing status, respectively. The possible effect of the treatment regimens on Schistosoma worms was evaluated by recording percentage of the recovered worms, tissue egg and oogram pattern. Result showed that, protection with AGE and NSO prevented most of the hematological and biochemical changes and markedly improved the antioxidant capacity of schistosomiasis mice compared to the infected-untreated ones. In addition, remarkable reduction in worms, tissue eggs and alteration in oogram pattern were recorded in all the treated groups. The antioxidant and antischistosomal action of AGE and NSO was greatly diverse according to treatment regimens. These data point to these compounds as promising agents to complement schistosomiasis specific treatment.

O propósito deste estudo foi verificar os efeitos anti-oxidantes e anti-esquistossômicos do extrato de alho (AGE) e do óleo da Nigella sativa (NSO) em camundongos normais e infectados com S. mansoni. AGE (125 mg/kg, i.p. ) e NSO (0,2 mg/kg, i.p.) foram administrados separadamente ou em combinação por 28 dias sucessivos começando do primeiro dia pós infecção (p.i.). Todos os camundongos foram sacrificados sete semanas p.i. Parâmetros hematológicos e bioquímicos incluindo funções renais e hepáticas foram medidos para avaliar o progresso da anemia e a possibilidade de dano tecidual. O nível total de proteínas séricas, albumina, globulina e colesterol foram também medidos. Níveis de malondialdeído (MDA) e glutationa (GSH) foram determinados em tecido hepático como biomarcações para o estado oxidativo e redutor, respectivamente. O possível efeito dos tratamentos sobre os vermes de Schistosoma foram avaliados através do percentual de vermes recuperados, ovos no tecido e o oograma. Resultados mostraram que a proteção com AGE e NSO preveniu a maior parte das alterações hematológicas e bioquímicas e melhoraram bastante a capacidade anti-oxidante de camundongos com esquistossomose comparados com aqueles infectados e não tratados. Adicionalmente, foi registrado uma acentuada redução nos vermes, ovos no tecido e alterações do oograma. A ação anti-oxidante e anti-esquistossômica do AGE e NSO foi diferente de acordo com os vários tratamentos. Estes dados mostram que estes compostos são agentes promissores para complementar o tratamento específico da esquistossomose.

Anti-tumor properties of blackseed (Nigella sativa L. ) extracts

The objective of the present study was to evaluate the in vitro and in vivo anti-cancer effect of Nigella sativa L. seed extracts. The essential oil (IC50 = 0.6 percent, v/v) and ethyl acetate (IC50 = 0.75 percent) extracts were more cytotoxic against the P815 cell line than the butanol extract (IC50 = 2 percent). Similar results were obtained with the Vero cell line. Although all extracts had a comparable cytotoxic effect against the ICO1 cell line, with IC50 values ranging from 0.2 to 0.26 percent (v/v), tests on the BSR cell line revealed a high cytotoxic effect of the ethyl acetate extract (IC50 = 0.2 percent) compared to the essential oil (IC50 = 1.2 percent). These data show that the cytotoxicity of each extract depends on the tumor cell type. In vivo, using the DBA2/P815 (H2d) mouse model, our results clearly showed that the injection of the essential oil into the tumor site significantly inhibited solid tumor development. Indeed, on the 30th day of treatment, the tumor volume of the control animals was 2.5 ± 0.6 cm³, whereas the tumor volumes of the essential oil-treated animals were 0.22 ± 0.1 and 0.16 ± 0.1 cm³ when the animals were injected with 30 µL (28.5 mg)/mouse and 50 µL (47.5 mg)/mouse per 48 h (six times), respectively. Interestingly, the administration of the essential oil into the tumor site inhibited the incidence of liver metastasis development and improved mouse survival.

Biochemical effects of Nigella sativa L seeds in diabetic rats.

Oral administration of ethanol extract of N. sativa seeds (300 mg/kg body weight/day) to streptozotocin induced diabetic rats for 30 days significantly reduced the elevated levels of blood glucose, lipids, plasma insulin and improved altered levels of lipid peroxidation products (TBARS and hydroperoxides) and antioxidant enzymes like catalase, superoxide dismutase, reduced glutathione and glutathione peroxidase in liver and kidney. The results confirm the antidiabetic activity of N. sativa seeds extract and suggest that because of its antioxidant effects its administration may be useful in controlling the diabetic complications in experimental diabetic rats.

study of the effects of garlic [Allium Sativum] and black seed [Nigella Sativa] on some liver functions and histopathology in nerium oleander induced hepatotoxicity in albino rats

The aim of the present study is the evaluation of possible hepatoprotective effects of Garlic and Nigella extract in albino rats. Nerium oleander plant is widely cultivated in Egypt and is considered the major cause of children's admission to hospital after accidental ingestion. Previous studies indicated that the plant produced impairment of hepatic and renal function. In the present study we investigated the possible effects of both oily extracts of garlic [Allium sativum, 6.6 mg/kg, orally] and black seed [Nigella sativa oil [NSO] 100 mg/kg, orally] on some hepatic toxic effects that were induced by intraperitoneal injection [i.p.] of Nerium oleander dried leaves extract [10 mg/kg] for 10 and 20 days. The results of this study were divided into three parts as follows: The first one of study showed that daily intraperitoneal injection [i.p.] of Nerium oleander leaves extract, sublethal dose [10 mg/kg] for 10 and 20 days produced a significant increase in liver enzymes activities [AST, ALT and ALP] whereas, albumin and albumin / globulin ratio were significantly decreased in 20 days while total proteins, globulin were not significantly increased in both 10 and 20 days. Histopathology of liver showed marked toxic manifestation on hepatocytes in the form of nuclear fragmentation [pyknotic]. The second one of the study showed that the simultaneous daily supplementation of garlic oily extract [6.6 mg/kg,orally] with [i.p] Nerium oleander extract [10 mg/kg, b.wt.] for 10 and 20 days produced significant reductions of liver enzymes AST and ALT whereas ALP was significantly reduced in 20 days. Albumin was significantly increased in 20 days. Total protein, globulin, albumin/globulin [ratio] were not significantly changed. Histopathology of liver showed marked improvement of hepatocytes and recovery changes are more marked in hepatic tissues. The third one showed that simultaneous daily supplementation of higella saliva oil [100 mg/kg] with [i.p.] Nerium oleander extract [10 mg /kg] for 10 and 20 days produced a significant reduction of alkaline phosphatase while all other parameters of the study were not significantly changed [10 days]. However, 20 days NSO produced significant reduction of AST, ALT, ALP, while albumin was significantly increased. As regards total proteins, globulin, albumin/globulin ratio, they were not significantly changed. Histopathology of the liver showed recovery manifestation of liver cells less than that observed with garlic extract. These results allow us to recommend the supplementation of either garlic or NSO or both in toxic liver affection disorders