Black cumin seed (Thymoquinone)

 

• HIF (Hypoxia Inducing Factor), a key pathway activated in RCC, is inhibited by Thymoquinone (Black Seed Oil) and Allicin (Garlic).  

• Thymoquinone selectively kills hypoxic renal cancer cells by suppressing HIF-1α-mediated glycolysis. 

• Thymoquinone induces apoptosis of human renal carcinoma Caki-1 cells by inhibiting JAK2/STAT3 through pro-oxidant effect.

• Thymoquinone inhibits the metastasis of renal cell cancer cells by inducing autophagy via AMPK/mTOR signaling pathway.

• Thymoquinone reduced the tumor xenograft growth of Caki-1 cells in nude mice.

• Antiviral. Helps with allergies. Improves memory. Renoprotective. 

Thymoquinone induces apoptosis of human renal carcinoma Caki-1 cells by inhibiting JAK2/STAT3 through pro-oxidant effect, 2020

Cancer cell-intrinsic reactive oxygen species (ROS) can be a weapon of RCC treatment. In the present study, we found that the phytochemical thymoquinone (TQ), a bioactive natural product obtained from the black cumin seeds of Nigella sativa, generates intracellular ROS in human renal cancer Caki-1 cells. Treatment of Caki-1 cells with high concentration of TQ up-regulated pro-apoptotic p53 and Bax expression, while downregulated anti-apoptotic Bcl-2 and Bcl-xl expression. Simultaneously, TQ suppressed the pro-oncogenic JAK2/STAT3 pathway, resulting in decreased expression of Bcl-2, Bcl-xl, cyclin D1, cyclin D2, and survivin. Thus, TQ can integrate between apoptosis and the pro-survival JAK2/STAT3 pathway through the Bcl family members, collectively magnifying Caki-1 cell apoptosis. However, treatment with the ROS scavenger N-acetyl cysteine significantly blocked TQ-induced apoptosis as well as incorporated signaling pathways, supporting that its pro-oxidant property is crucial for Caki-1 cell apoptosis. Moreover, TQ reduced the tumor xenograft growth of Caki-1 cells in nude mice. Taken together, these data suggest that TQ is a prominent anti-cancer drug to treat human RCC by enhancing apoptosis through its pro-oxidant nature.

Thymoquinone selectively kills hypoxic renal cancer cells by suppressing HIF-1α-mediated glycolysis, 2019

Several reports have shown that thymoquinone (TQ) effectively attenuates angiogenesis in cancer cells, resulting in suppression of tumor growth. However, it is not yet clear whether TQ reduces hypoxia-inducible factor-1α (HIF-1α) expression in hypoxic cancer cells. Here, we found that TQ was a novel HIF-1α inhibitor through hypoxia response element (HRE)-luciferase assay-based large screening by using 502 natural compounds containing chemical library. TQ reduced HIF-1α protein levels in renal cancer cells; however, it did not affect the HIF-1α protein levels in the presence of proteasome inhibitor, MG132, indicating that the reduction effects of TQ on HIF-1α protein are mediated via the ubiquitination-proteasome dependent pathway. TQ boosted HIF-1α protein degradation, and the mechanism was revealed by inhibiting interaction between HSP90 and HIF-1α. TQ suppressed downstream genes of HIF-1α, indicating negative impact of TQ on HIF-1α transcriptional activities. In addition, TQ altered glucose, lactate, and ATP levels, leading to anaerobic metabolic disturbance. TQ induced apoptosis in hypoxic cancer cells as determined by crystal violet staining and flow cytometry for annexin V-stained cells. Taken together, we suggested that TQ is a potential anticancer agent targeting HIF-1α.

Thymoquinone inhibits the metastasis of renal cell cancer cells by inducing autophagy via AMPK/mTOR signaling pathway, 2018

Thymoquinone a bioactive constituent extracted from the seeds of Nigella sativa, has been proved to exert anti-tumor efficiency in various cancers. Autophagy is a self-digestion phenomenon, and its role in tumor formation and progression remains controversial. In the present study, we investigated the effects of TQ on renal cell cancer (RCC) cell lines (786-O and ACHN) using wound healing assay, transwell assay and western blot analysis. We found that TQ effectively inhibited the metastatic capacity of RCC cells in vitro, which was also verified in a xenograft model. Meanwhile, we observed LC3 puncta and detected the expression of LC3 in TQ-treated RCC cells, and then found that autophagy was induced by TQ in 786-O and ACHN cell lines. In addition, TQ inhibited the migration and invasion as well as the EMT in RCC cells in an autophagy-dependent manner. To further explore the underlying mechanism, we detected the AMPK/mTOR signaling pathway. The results indicated that TQ inhibited the metastasis of RCC cells by inducing autophagy via AMPK/mTOR signaling pathway. In conclusion, our findings provide a novel therapeutic strategy that aims at TQ-induced autophagy in RCC treatment.

Nigella sativa L. (Black Cumin): A Promising Natural Remedy for Wide Range of Illnesses, 2019 <- this paper has a lot of interesting stuff (T2D, HBP etc)

4.6.3. Antiviral Activity

N. sativa seed oil was found to suppress viral load in murine model: cytomegalovirus infected mice to undetectable level in the liver and spleen in 10 days' intraperitoneal administration. This was possibly due to the increase in number and function of CD4+ve T cells and increased production of interferon- (INF-) gamma [115]. Interestingly, patients (30) with hepatitis C virus (HCV) infection, who were not eligible for IFN-α/ribavirin therapy showed significant improvement in HCV viral load (16.67% became seronegative and 50% showing significant decrement) and proved laboratory parameter like total protein, red blood cell, and platelet count, decreased fasting blood glucose, and postprandial glucose in both diabetic and nondiabetic HCV patients and reduced lower-limb edema after they are managed with black cumin seed oil [116].

According to a case report conducted by Onifade et al., after treatment with 10 mL of black seed twice daily for 6 months, a complete regaining and seroreversion of a 46-year-old HIV positive patient was evidenced [117]. In addition, a 27-year-old HIV infected woman was diagnosed during ante-natal care; she was not eligible for antiretroviral therapy; hence herbal therapist initiated her on black cumin and honey mixture (10 mL) thrice daily for a year. The repeat serology assessments for HIV infection became negative with undetectable viral load. The woman also got 3 children (2007, 2010, and 2012) that all were breastfed and none of the children infected with HIV and her repeat CD4 count was not less than 750 cells/μL [118]. Nowadays HIV/AIDS is a serious global threat and in this regard, N. sativa can be a promising natural therapy to cure such a chronic infectious disease, after validating its full therapeutic efficacy by further investigations.

Efficacy of Black Seed (Nigella sativa) and Lemon Balm (Melissa officinalis) on Non-Alcoholic Fatty Liver Disease: A Randomized Controlled Clinical

Fifty participants with the condition took a daily supplement mixture consisting of 20mg black seed and lemon balm for 18 months. Compared to placebo, the treatment group experienced a significant reduction in liver enzymes (AST and ALT) and grade of fatty liver. There was a more significant reduction in the grade of fatty liver over the study period in the intervention group compared with the control group (0.58 ± 0.50 versus 1.51 ± 0.54, P < 0.001).

Conclusion: Traditional Persian Medicine-based preparations of Nigella sativa and Melissa officinalis could reduce body weight and liver enzymes and improves the grade of fatty liver in Non-Alcoholic Fatty Liver Disease.

Thymoquinone Renal Protective

37) Al Fayi, Majed, et al. “Thymoquinone and curcumin combination protects cisplatin-induced kidney injury, nephrotoxicity by attenuating NFκB, KIM-1 and ameliorating Nrf2/HO-1 signalling.” Journal of drug targeting 28.9 (2020): 913-922.

38) Abdel-Daim, Mohamed M., et al. “Thymoquinone and diallyl sulfide protect against fipronil-induced oxidative injury in rats.” Environmental Science and Pollution Research 25.24 (2018): 23909-23916.

39) Ragheb, Ahmed, et al. “The protective effect of thymoquinone, an anti-oxidant and anti-inflammatory agent, against renal injury: a review.” Saudi Journal of Kidney Diseases and Transplantation 20.5 (2009): 741.

Natural source of Thymoquinone?

Black cumin seeds from Amazon are cheap. 

Other effects (examine.com)

• ​​An increase in serum albumin has been noted, and the reason for this currently unknown.

• Nasal congestion as a side-effect of allergic rhinitus is slightly reduced following the treatment of rhinitus.

• Seizure frequency in children with poorly controlled epilepsy is significantly reduced with a seed extract.

• Pain as a side-effect of rheumatoid arthritis is modestly reduced.

• There appears to be a small but respectable (15-20% higher than baseline) improvement in logical memory and 30 minute recall in older subjects supplementing the seeds in their daily lifestyle.

• Although only based on one study, in men with central obesity and a wide variety of general health complaints supplementation has outright abolished all measured complaints such as loss of libido, high appetite, pain, and forgetfulness.

• Supplementation of the seed appears to beneficially influence most symptoms associated with allergies and most causes of the allergies (rhinitus, eczema, asthma, etc.), with the magnitude being somewhat notable among supplements.

• A pilot study in hepatitis C noted that the viral load was reduced to 38.6% of baseline with a modest dosage of the seed oil, a fairly drastic reduction.

Inhibits JAK2 across 6 different cancers:

• Induces apoptosis in human colon cancer HCT116 cells through inactivation of STAT3 by blocking JAK2- and Src-mediated phosphorylation of EGF receptor tyrosine kinase (link)

• Induces apoptosis of human renal carcinoma Caki-1 cells by inhibiting JAK2/STAT3 through pro-oxidant effect (link)

• Augments Cisplatin-Induced Apoptosis on Esophageal Carcinoma Through Mitigating the Activation of JAK2/STAT3 Pathway (link)

• Induces oxidative stress-mediated apoptosis through downregulation of Jak2/STAT3 signaling pathway in human melanoma cells (link)

• Inhibits proliferation in gastric cancer via the STAT3 pathway in vivo and in vitro (link)

• Inhibits proliferation, induces apoptosis and chemosensitizes human multiple myeloma cells through suppression of signal transducer and activator of transcription 3 activation pathway (link)

Healthline (link):

• One study in 80 adults with asthma found that taking 500 mg of black seed oil capsules twice a day for 4 weeks significantly improved asthma control (16).

• In one 8-week study, 90 women ages 25–50 with obesity were given a low calorie diet and either a placebo or 1 gram of black seed oil per meal for a total of 3 grams per day (21). At the end of the study, those taking the black seed oil had lost significantly more weight and waist circumference than the placebo group. The oil group also experienced significant improvements in triglyceride and LDL (bad) cholesterol levels.

• Several studies in individuals with type 2 diabetes indicate that a dose of 2 grams per day of crushed whole black seeds may significantly reduce fasting blood sugar levels and hemoglobin A1c (HbA1c) levels, a measure of average blood sugar levels over 2–3 months (23, 24, 25).

•  While most studies use black seed powder in capsules, black seed oil has also been shown to help lower blood sugar levels (25).

• One study in 99 adults with type 2 diabetes found that both 1/3 teaspoon (1.5 mL) and 3/5 teaspoon (3 mL) per day of black seed oil for 20 days significantly reduced HbA1c levels, compared with a placebo (26).

• Two studies, one in 90 women with obesity and the other in 72 adults with type 2 diabetes, found that taking 2–3 grams of black seed oil capsules per day for 8–12 weeks significantly reduced LDL (bad) and total cholesterol levels (21, 28).

• Another study in 90 people with high cholesterol levels observed that consuming 2 teaspoons (10 grams) of black seed oil after eating breakfast for 6 weeks significantly reduced LDL (bad) cholesterol levels (29).

• One study in 70 healthy adults noted that 1/2 teaspoon (2.5 mL) of black seed oil twice a day for 8 weeks significantly reduced blood pressure levels, compared with a placebo (30).

• One study in 40 healthy older adults found significant improvements in measures of memory, attention, and cognition after taking 500 mg of N. sativa capsules twice a day for 9 weeks (35).

• Limited research suggests that black seed oil may improve semen quality in men diagnosed with infertility (44, 45).

• Due to its anti-inflammatory effects, limited research suggests that black seed oil may help reduce joint inflammation in people with rheumatoid arthritis (41, 42, 43).

Concerns:

• One potential concern is that black seed oil may interact with medications that are processed through the cytochrome P450 pathway. Common medications that could be affected include warfarin (Coumadin) and beta-blockers like metoprolol (Lopressor) (49, 50).

• There’s also concern that taking too much black seed oil could harm your kidneys. In one reported case, a woman with type 2 diabetes was hospitalized for acute kidney failure after taking 2–2.5 grams of black seed capsules daily for 6 days (51).

• However, other studies haven’t shown negative effects on kidney health. In fact, some studies have even suggested that black seed oil has a protective effect on kidney function (2, 52, 53).

Effects of Nigella sativa oil with a low-calorie diet on cardiometabolic risk factors in obese women: a randomized controlled clinical trial, 2015

Females aged 25-50 years old with body mass index (BMI) between 30 and 35 kg m(-2). They were randomly assigned to receive a low-calorie diet with 3 g per day (1 g before each meal) NS oil or placebo for 8 weeks. Anthropometric indices, dietary intake and biochemical parameters were measured at the baseline and after the intervention. Eighty-four females completed the trial (intervention n = 43, placebo n = 41). Two groups were similar in the baseline characteristics. After the intervention, dietary intake was changed in both groups compared to the baseline, but the differences were not significant between the two groups. In the NS group, weight (-6.0 vs. -3.6%; p < 0.01) and waist circumference (-6.9 vs. -3.4%; p < 0.01) decreased significantly compared with the placebo group at the end of the trial. Comparison of biochemical parameters presented a significant decline in triglyceride (-14.0 vs. 1.4%; p = 0.02) and very low density lipoprotein (-14.0 vs. 7%; p < 0.01) levels in the NS group compared to the placebo group. NS oil concurrent with a low-calorie diet can reduce cardiometabolic risk factors in obese women.

A systematic review and meta-analysis of randomized controlled trials investigating the effects of supplementation with Nigella sativa (black seed) on blood pressure, 2016

Total 11 RCTs, including 860 hypertensive or normotensive individuals were eligible, of which 10 compared N. sativa versus placebo and one versus standard treatment. SBP and DBP means decreased from 132.85 to 125.19 mmHg and from 82.63 to 77.74 mmHg after mean treatment duration of 8.3 weeks in N. sativa groups, respectively. The difference in reductions as compared with control/standard groups were -3.26 (-5.10, -1.42; I = 59%) mmHg in SBP and -2.80 (-4.28, -1.32; I = 60%) mmHg in DBP.

The effect of Nigella sativa L. supplementation on serum C-reactive protein: A systematic review and meta-analysis of randomized controlled trials, 2019

Only five articles which reported data of interest entered for data analysis. The meta-analysis showed a significant reduction in serum CRP (WMD: -0.55 mg/L, 95% CI: -1.02, -0.08, P = 0.02), with significant heterogeneity between selected studies (I2 = 77.3%). Between-study heterogeneity disappeared following subgroup analysis, stratified by baseline BMI (≥30 kg/m2: I2 = 2.8%). However, the effect of N. sativa seed and seed oil supplementation on CRP was only significant in studies that were conducted on participants with BMI ≥ 30 kg/m2 (WMD: -0.50 mg/L, 95% CI: -0.85, -0.15).

The effect of Nigella sativa on the measures of liver and kidney parameters: A systematic review and meta-analysis of randomized-controlled trials, 2020

Nineteen trials (n = 1295 participants) were included in the meta-analysis. We observed that N.S supplements had significant reducing effects on alkaline-phosphatase (ALP) [9 trials, n = 710 participants, weighted mean difference (WMD)= -10.825; 95 %CI: -19.658, -1.992 U/L; P = 0.016; I2 = 75.7 %; P-heterogeneity = 0.000) and blood urea nitrogen (BUN) (12 trials, n = 821 participants, WMD= -1.016; 95 % CI: -1.760, -0.273 U/L; P = 0.007; I2 = 87.7 %; P-heterogeneity = 0.000) concentrations. Subgroup analysis showed that, an intervention of more than 12 weeks was found to have a reducing effect on aspartate- aminotransferase (AST) measures (2 trials, n = 201 participants, WMD= -11.317; 95 % CI: -15.007, -7.626; P = 0.000; I2 = 0.0 %; P-heterogeneity = 0.977). Creatinine levels increased significantly in studies that considered adjusted analysis based on covariates (3 trials, n = 152 participants, WMD = 0.070; 95 % CI: 0.027, 0.112 U/L; P = 0.001; I2 = 0.0 %; P-heterogeneity = 0.788). A daily dose of 1100-1500 mg of N.S supplements was observed to have a substantial reducing effect on ALP levels (5 trials, n = 340 participants, WMD= -11.323; 95 % CI: -21.418, -1.229 U/L; P = 0.028; I2 = 0.00 %; P-heterogeneity = 0.686), while a dosage of more than 2000 mg per day led to a significant increase in BUN concentrations (2 trials, n = 101 participants, WMD= -1.016; 95 % CI: -1.760, -0.273 U/L; P = 0.007; I2 = 87.7 %; P-heterogeneity = 0.000). Our data suggested that N.S supplementation had significant impacts on liver and kidney parameters leading to a decrease in ALP and BUN levels. Longer duration of intervention and normal daily dosages of N.S supplements led to significant reductions in ALP and AST concentrations, respectively, while higher daily dosages increased BUN levels.

Effects of Nigella sativa on glycemic control, lipid profiles, and biomarkers of inflammatory and oxidative stress: A systematic review and meta-analysis of randomized controlled clinical trials, 2020

A total of 50 trials were included in this meta-analysis. We found a significant reduction in total cholesterol (WMD: -16.80; 95% CI: -21.04, -12.55), triglycerides (WMD: -15.73; 95% CI: -20.77, -10.69), LDL-cholesterol (WMD: -18.45; 95% CI: -22.44, -14.94) and VLDL-cholesterol (WMD: -3.72; 95% CI: -7.27, -0.18) following supplementation with N. sativa. In addition, there was significant reductive effect observed with N. sativa on fasting glucose (WMD: -15.18; 95% CI: -19.82, -10.55) and HbA1C levels (WMD: -0.45; 95% CI: -0.66, -0.23). Effects of N. sativa on CRP (WMD: -3.61; 95% CI: -9.23, 2.01), TNF-α (WMD: -1.18; 95% CI: -3.23, 0.86), TAC (WMD: 0.31; 95% CI: 0.00, 0.63), and MDA levels (WMD: -0.95; 95% CI: -2.18, 0.27) were insignificant. This meta-analysis demonstrated the beneficial effects of N. sativa on fasting glucose, HbA1c, triglycerides, total-, VLDL-, LDL-cholesterol levels.