Synergistic effects of medicinal plants in combination with spices from algeria: Anticancer, antiangiogenic activities, and embrytoxicity studies.

ETHNOPHARMACOLOGICAL RELEVANCE: Bryonia dioica Jacq., Evernia prunastri (L.) Ach., Telephium imperati L., and Aristolochia longa L. are species widely used in traditional medicine to treat several diseases including cancer. Conjugation of two or more extracts is an approach to improve the effectiveness of their pharmacological activities. AIM OF THE STUDY: To evaluate the synergistic anticancer and anti-angiogenic effects of medicinal plants and edible species combinations. MATERIALS AND METHODS: In this work, B. dioica, E. prunastri, Telephium imperati, and Aristolochia longa extracts were conjugated to form four mixtures. The antiproliferative effect of mixtures on several carcinoma cells was examined by MTT assay, and the antiangiogenic activity was estimated through Hen's egg test in vivo. Moreover, in an Ovo model, 35 fertilized Ross eggs were used to test the embryotoxicity of mixtures. RESULTS: At the highest concentration of 200 µg/mL, both mixtures exerted an important cytotoxic effect against human carcinoma cells. The mixture BETE (Bryonia Evernia Telephium Extract) significantly reduced HT-29, PC-3, and A-549 cell viability. Likewise, this mixture strongly suppressed vascularization in vivo at 200 µg/mL. Interestingly, no signs of toxicity on Perdix embryos were recorded within 21 days of treatment. More importantly, the mixture did not have any cytotoxic effect on non cancerous cells. CONCLUSION: Taken together, our results suggest that the synergy between B. dioica, E. prunastri and T. imperati may be promising for developing new anti-cancer treatments.

Medicinal Plants Used by Traditional Healers in Algeria: A Multiregional Ethnobotanical Study.

Traditional medicine is the cornerstone that boosts scientific research to explore new therapeutic approaches. The study aimed to assess the traditional knowledge and use of medicinal plants to treat various ailments by Algerian traditional healers. Forty traditional healers were face-to-face interviewed in three different Algerian areas (West, Kabylia, and Sahara). The data collected were analyzed using quantitative indices such as fidelity level (FL) and informant consensus factor (FIC). A total of 167 species belonging to 70 families were recorded. Lamiaceae (13%), Asteraceae (13%), Apiaceae (7%), and Rosaceae and Fabaceae (5% each) were the most cited families. The survey revealed that leaves were the most used parts of the plants (29%). Furthermore, decoction (35%), raw (24%), and infusion (19%) were the common modes for the remedies' preparation. Here, 15% of the total species were newly reported as medicinal plants. Besides, it was reported for the first time a total of 47 new therapeutic uses for 20 known plant species. Of 17 ailments categories, cancer was presented by 44 species, showing the highest FIC of 0.46. Marrubium vulgare L., Artemisia herba-alba Asso., Zingiber officinale Roscoe., and Juniperus phoenicea L. recorded the maximum fidelity value of 100%. Therefore, our study reveals strong ethnomedicinal knowledge shared by local populations living in the three regions studied. The medicinal species with a high FL could be promising candidates for identifying new bioactive molecules.

Lower p66Shc promoter methylation in subjects with chronic renal failure.

OBJECTIVE: To determine the correlation between DNA methylation of p66Shc promoter and some markers of inflammatory and oxidative stress in chronic renal failure (CRF) patients compared with healthy subjects. METHODS: An observational cross-sectional study was conducted in the nephrology department at Sidi Bouzid Regional Hospital (Tunisia). In total, 39 patients with CRF and 37 healthy subjects were included. Several biochemical parameters were measured. Furthermore, markers of the oxidative and inflammatory status (MDA, TAS, SOD, and CRP) were evaluated. The p66Shc methylation status was determined using the methylation-specific PCR. RESULTS: Our results showed that levels of blood glucose, urea, creatinine, uric acid, ChT, TG, albuminuria, CRP and MDA were significantly elevated in CRF patients compared to controls. Furthermore, p66Shc promoter region was highly demethylated in CRF patients compared to healthy controls (84% vs 4%). Our data showed a positive correlation between p66Shc hypomethylation and levels of MDA (r = 0.93; p<0, 05) and CRP (r = 0.89; P <0, 05), as well as a significant negative correlation between p66Shc hypomethylation, TAS (r = -0.76; P <0, 05) and SOD (r = -0.77; p<0, 05) levels. Similarly, there was a positive correlation between p66Shc hypomethylation and the disease stages. Importantly, multiple regression analysis showed that p66shc DNA hypomethylation remains strongly correlated with MDA, CRP and stages of CRF. CONCLUSION: This study indicates that the DNA hypomethylation of p66shc promoter was correlated with oxidative and inflammatory stress and the disease stages in CRF patients.

Medicinal Plants as Sources of Active Molecules Against COVID-19.

The Severe Acute Respiratory Syndrome-related Coronavirus 2 (SARS-CoV-2) or novel coronavirus (COVID-19) infection has been declared world pandemic causing a worrisome number of deaths, especially among vulnerable citizens, in 209 countries around the world. Although several therapeutic molecules are being tested, no effective vaccines or specific treatments have been developed. Since the COVID-19 outbreak, different traditional herbal medicines with promising results have been used alone or in combination with conventional drugs to treat infected patients. Here, we review the recent findings regarding the use of natural products to prevent or treat COVID-19 infection. Furthermore, the mechanisms responsible for this preventive or therapeutic effect are discussed. We conducted literature research using PubMed, Google Scholar, Scopus, and WHO website. Dissertations and theses were not considered. Only the situation reports edited by the WHO were included. The different herbal products (extracts) and purified molecules may exert their anti-SARS-CoV-2 actions by direct inhibition of the virus replication or entry. Interestingly, some products may block the ACE-2 receptor or the serine protease TMPRRS2 required by SARS-CoV-2 to infect human cells. In addition, natural products were shown to inhibit the SARS-CoV-2 life-cycle related proteins such as papain-like or chymotrypsin-like proteases. In conclusion, we suggest that natural products could be used alone or in combination as alternative medicines to treat/prevent COVID-19 infection. Moreover, their structures may offer clues for the development of anti-SARS-CoV-2 drugs.

Pre-exposure and Post-exposure new prophylactic treatments against COVID-19 in healthcare workers

The Severe Acute Respiratory Syndrome-related Coronavirus 2 or novel coronavirus (COVID-19) infection pandemic continues to spread. Since the outbreak of the COVID-19 in Wuhan (China), healthcare workers have been infected and are considered at high risk of contamination. Moreover, in addition to the physical effects of COVID-19, the pandemic results in important mental health issues among healthcare workers such as anxiety, stress, depression, and further nervous or mental disorders. Despite the increasing number of clinical trials aiming to develop vaccines or test antiviral molecules, till now no efficient anti- SARS-CoV-2 drugs have been validated. The COVID-19 pandemic led us to call for an urgent nutritional intervention model that should be established to prevent and/or reduce the negative impact of COVID-19 on healthcare workers. In the present paper, we suggest a safe nutritional supplementation of MgZn- B vitamins (B1, B6, B9, and B12) in healthcare workers as pre-exposure and post-exposure new prophylactic treatments. Furthermore, the paper reports the scientific arguments and the possible mechanisms by which the Mg-Zn- B vitamins supplementation may exert its beneficial effects in the healthcare workers facing the COVID-19 pandemic. Overall, the Mg-Zn- B vitamins supplementation would enhance the immune response against SARS-CoV2, prevent inflammatory processes and oxidative stress, fight or alleviate the COVID-19-related mental health issues, or even reduce the replication. Each element of the supplementation possesses important and promising effects contributing to the possible efficiency of the suggested Mg-ZnB vitamins supplementation in healthcare workers

Gene surgery: Potential applications for human diseases.

Gene therapy became in last decade a new emerging therapeutic era showing promising results against different diseases such as cancer, cardiovascular diseases, diabetes, and neurological disorders. Recently, the genome editing technique for eukaryotic cells called CRISPR-Cas (Clustered Regulatory Interspaced Short Palindromic Repeats) has enriched the field of gene surgery with enhanced applications. In the present review, we summarized the different applications of gene surgery for treating human diseases such as cancer, diabetes, nervous, and cardiovascular diseases, besides the molecular mechanisms involved in these important effects. Several studies support the important therapeutic applications of gene surgery in a large number of health disorders and diseases including ß-thalassemia, cancer, immunodeficiencies, diabetes, and neurological disorders. In diabetes, gene surgery was shown to be effective in type 1 diabetes by triggering different signaling pathways. Furthermore, gene surgery, especially that using CRISPR-Cas possessed important application on diagnosis, screening and treatment of several cancers such as lung, liver, pancreatic and colorectal cancer. Nevertheless, gene surgery still presents some limitations such as the design difficulties and costs regarding ZFNs (Zinc Finger Nucleases) and TALENs (Transcription Activator-Like Effector Nucleases) use, off-target effects, low transfection efficiency, in vivo delivery-safety and ethical issues.

Bryonia dioica aqueous extract induces apoptosis and G2/M cell cycle arrest in MDA­MB 231 breast cancer cells.

Bryonia dioica Jacq. is a climbing perennial herb with tuberous roots which is widely used in traditional medicine in Algeria for the treatment of cancer. The present study aimed to evaluate the apoptogenic activity and phytochemical composition of the aqueous extract of B. dioica roots growing in Algeria. The cytotoxic effect of B. dioica aqueous decoction against breast cancer MDA­MB­231 cells was evaluated by an MTT assay. Apoptosis induction was assessed by an Annexin V­fluorescien iosthiocyanate assay. Propidium iodide staining of cell DNA was used to assess the effects on the cell cycle. In addition to UV­Visible (UV­vis) analysis, the major compounds of the extracts were determined using liquid chromatography­mass spectrometric analyses. Our results showed that the B. dioica aqueous extract induced cell death in a time­dependent manner. The highest inhibitory effect was produced at concentrations of 50 µg/ml or higher after 72 h of treatment (91.15±0.71%). Furthermore, the extract induced apoptosis of MDA­MB­231 cells. At 250 µg/ml, 64.61% of the treated MDA­MB­231 cells were apoptotic. This was accompanied by cell cycle arrest at G2/M phase. The percentage of cells in G2/M increased from 15.7% (untreated cells) to 59.13% (50 µg/ml) and 58.51% (250 µg/ml). The UV­vis absorption spectra of B. dioica aqueous extract showed two absorption bands characteristic of the flavonol skeleton; 350­385 nm (Band I) and 250­280 nm (Band II). Myricetin (2,5,7,3,4,5­pentahydroxylflavonol) was found to be the major compound in the B. dioica aqueous extract. These findings suggest that B. dioica could be considered a promising source for developing novel therapeutics against breast cancer.

Colorectal cancer and medicinal plants: Principle findings from recent studies.

Colorectal cancer is one of the most frequent malignancies in the world. Although recent advances in chemotherapy have improved management and survival of colorectal cancer patients, side effects and resistance to chemotherapy have shown the limitations of current chemotherapy and led to the search for alternative treatments. In this context, medicinal plants provide a large number of molecules with proven cytotoxic and apoptogenic activities against several types of cancers including colorectal cancer. These molecules belong to various phytochemical families and trigger different signaling pathways. Here, we review the recent findings regarding the anti-colorectal cancer activities of several plants, both in vitro and in vivo, and the phytochemical molecules possibly responsible for these activities. Besides, their effects on several cancer signaling pathways are discussed. This review highlights the importance of medicinal plants as promising sources of lead anti-colorectal molecules.

Phytochemical analysis, antioxidant and anti-Candida albicans activities of Annona cherimola Mill. fruit pulp

Aims: The main objectives of the present study were to characterize the phytochemical profile of Annona cherimola Mill, to assess its antioxidant characteristics and its antifungal activity against Candida albicans. Methods and Material: Aqueous decoction, aqueous infusion, aqueous maceration, and methanolic maceration were screened for the presence of phytochemicals and to quantify content of phenolics, tannins, and flavonoids. Furthermore, antioxidant activity was assessed using DPPH and FRAP assays, as well the assessment of antifungal activity for the different extracts. Results: Results showed that phenols, tannins, flavonoids, and saponins were present in the four extracts. The aqueous maceration extract presented the highest total phenolic content (3.687 mg GAE/g of extract). Decoction extract showed the lowest phenolic content 2.504 mg GAE/g. Besides, infusion showed the most important total flavonoids content (2.567mg CE/g). The most relevant total antioxidant activity was found for decoction (lowest IC50 12.61 mg/ml AAE). The aqueous maceration exhibited the less antioxidant activity (IC50= 21.98 mg/ml AAE). The best scavenging activity was observed for decoction (IC50=7.27 mg/mL). All the extracts showed a reducing capacity. Infusion exhibited the best reducing power (EC50 = 11.29 mg/mL), compared to decoction (EC50 = 39.32 mg/mL). Regarding antifungal activity, at 100 and 200 µg/mL, decoction and methanolic maceration resulted in 6 and 9 mm inhibition zone, respectively. In addition, at higher doses (800 and 2000 µg/mL), inhibition zone increased in a dose dependent manner for all the extracts. Conclusions: Annona cherimola Mill. could be an important source of bioactive molecules with antioxidant and antifungal activities

Medicinal plants used by traditional healers from South-West Algeria: An ethnobotanical study.

BACKGROUND/AIM: This study aimed to document and analyzes the local knowledge of medicinal plants' use by traditional healers in South-west Algeria. METHODS: The ethnobotanical survey was conducted in two Saharian regions of South-west of Algeria: Adrar and Bechar. In total, 22 local traditional healers were interviewed using semi-structured questionnaire and open questions. Use value (UV), fidelity level (FL), and informant consensus factor (FIC) were used to analyze the obtained data. RESULTS: Our results showed that 83 medicinal plants species belonging to 38 families are used by traditional healers from South-west of Algeria to treat several ailments. Lamiaceae, Asteraceae, Apiaceae, and Fabaceae were the most dominant families with 13, 8, 6, and 4 species, respectively. Leaves were the plant parts mostly used (36%), followed by seeds (18%), aerial parts (17%) and roots (12%). Furthermore, a decoction was the major mode of preparation (49%), and oral administration was the most preferred (80%). Thymus vulgaris L. (UV = 1.045), Zingiber officinale Roscoe (UV = 0.863), Trigonella foenum-graecum L. (UV=0.590), Rosmarinus officinalis L. (UV = 0.545), and Ruta chalepensis L. (UV = 0.5) were the most frequently species used by local healers. A great informant consensus has been demonstrated for kidney (0.727), cancer (0.687), digestive (0.603), and respiratory diseases. CONCLUSION: This study revealed rich ethnomedicinal knowledge in South-west Algeria. The reported species with high UV, FL, and FIC could be of great interest for further pharmacological studies.

Ethnobotanical study of medicinal plants used by traditional healers in Mascara (North West of Algeria).

ETHNOPHARMACOLOGICAL RELEVANCE: Medicinal plants are considered as a rich source of bioactive compounds. The present study aimed to document the local knowledge of medicinal plants' use by traditional healers in Mascara, North-west Algeria. MATERIALS AND METHODS: The present study was carried out in Mascara (North West of Algeria). Ethnobotanical data were recorded from 43 traditional healers practicing in Mascara. Data collected was analysed using quantitative indices such as the use value (UV), fidelity level (FL) and Informant Consensus Factor (FIC). RESULTS: Traditional healers reported 141 medicinal plant species belonging to 54 families and 125 genera for the treatment of different ailments grouped into 14 ailments categories. Lamiaceae were the most represented family with 19 species (13.57%) followed by Asteracea, Apiaceae and Fabaceae. Thymus vulgaris L. was the most frequently used by local informants, with the highest UV of 0.883 (38 use reports). Our findings revealed that 39 species have not been previously reported as medicinal plants in the region. Furthermore, we report for the first time a total of 100 new therapeutic uses for 37 known plant species. FIC values ranged from 0.125 to 0.658. Gastro-intestinal diseases had the highest FIC (0.658) with 60 species and 261 use reports. CONCLUSION: The present study revealed the important local knowledge as showed by the variety of species used to treat several ailments. Recorded species with high UV should be subjects of further pharmacological studies to validate their popular use and to isolate the bioactive compounds.

Response of Bone Resorption Markers to Aristolochia longa Intake by Algerian Breast Cancer Postmenopausal Women.

Aristolochia longa is widely used in traditional medicine in Algeria to treat breast cancer. The aim of the present study was to investigate the response of bone resorption markers to A. longa intake by Algerian breast cancer postmenopausal women. According to the A. longa intake, breast cancer patients were grouped into A. longa group (Al) (n = 54) and non-A. longa group (non-Al) (n = 24). 32 women constituted the control group. Bone resorption markers (from urine) pyridinoline (PYD) and deoxypyridinoline (DPD) were determined by HPLC. Serum and urinary creatinine, uric acid, and urea were measured. 1 g of A. longa intake resulted in significant rise of renal serum markers and a pronounced increase of bone resorption markers. The intake of A. longa roots is detrimental for kidney function and resulted in high bone resorption, maybe due to the reduction in renal function caused by the aristolochic acids contained in the roots.

Ethnobotanical study, antifungal activity, phytochemical screening and total phenolic content of Algerian Aristolochia longa.

AIM: Aristolochia longa (from the family Aristolochiaceae) is widely used in Algerian traditional medicine. Here, we document ethnomedicinal uses by local population of Mascara province (West Algeria) and we evaluate the antifungal activity, the phytochemical composition and total phenolic content of aqueous extract (decoction) of the roots of A. longa from Algeria. MATERIALS AND METHODS: The ethnobotanical investigation was carried out in Mascara Province (West Algeria). Antifungal activity was assessed against Saccharomyces cerevisiae. Total phenolic content was measured using the Folin-Ciocalteu's reagent. RESULTS: Our results showed that A. longa is widely used to treat several ailments such as cancer (38%), skin infections (14%), and diabetes (11%). Crushed roots are commonly used (89%) mixed with honey, milk, water or other medicinal plants. A. longa aqueous extract induced growth inhibition of S. cerevisiae cells in a dose - and time - dependent manner. An effective suppression of S. cerevisiae (97.06% inhibition of proliferation) was obtained at the 500 µg/mL after 72 h. Results of the phytochemical screening revealed that A. longa aqueous extract contained various bioactive compounds, including polyphenols and flavonoids. Total phenolic content in A. longa aqueous extract was found to be 6.07 ± 0.12 mg (gallic acid equivalents)/g. CONCLUSION: A. longa may be considered as a promising source of new drugs for treating cancer and as a good antifungal agent.

Cancer incidence in North West Algeria (Mascara) 2000-2010: results from a population-based cancer registry.

Cancer is a leading cause of death worldwide accounting for 7.4 million deaths. Cancer has become a major public health concern in Algeria. The aim of the present study was to estimate cancer incidence in Mascara Province based on the population-based cancer registry. We analyzed data from the cancer registry of Mascara covering all cancer cases diagnosed by all methods and included in the registry from 1(st) January 2000 to 31(st) December 2010. The results are presented as incidence rates of cases by site, sex, age, and crude rate. Age-standardized rates per 100,000 person-years (ASRs) were calculated, using the direct method of standardization to the world population. A total of 1875 cases of invasive cancer were recorded. The mean age of diagnosis for all cancers was 52.66 ± 0.5 in men and 59.18 ± 0.6 in women. The ASR for all cancers in females was 27.8 per 100,000, and that for males was 23.6 per 100,000. The most important finding of the present study was the high incidence of liver cancer among males and females in Mascara. Among females, breast cancer was the most frequently reported followed by Cervix uteri, liver and colon. The most frequent cancer types in males were lung, colon, esophagus and stomach and liver. Cancer incidence in Mascara province was lower than that reported in other national and regional registries. Findings of the present study revealed high incidence of liver cancer in the province, the highest in Algeria, suggesting high prevalence of risk factors.

Bryonia dioica aqueous extract induces apoptosis through mitochondrial intrinsic pathway in BL41 Burkitt's lymphoma cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Bryonia dioica Jacq. is a climbing perennial herb with tuberous roots which is widely used in traditional medicine in Algeria for the treatment of cancers; it belongs to the genus Bryonia (Cucurbitaceae). AIM OF THE STUDY: To investigate the cytotoxic and apoptogenic activities, the phytochemical composition and acute toxicity of the aqueous extract of Bryonia dioica roots growing in Algeria. MATERIALS AND METHODS: Dried roots of Bryonia dioica were extracted with water (decoction). The cytotoxic effects of the aqueous extract in the Burkitt's lymphoma BL41 cell lines were evaluated by flow cytometry. Apoptosis induction was assessed by two corroborative assays; propidium iodide (PI) staining of cell DNA and flow cytometric light scatter analysis. The mitochondria membrane potential was investigated using a fluorescent dye DIOC6. The expression of caspases-3, -8, -9 and PARP was assessed by Western blot. The phytochemical screening of the roots of Bryonia dioica was performed using qualitative phytochemical standard procedures. RESULTS: The Bryonia dioica aqueous extract induced cell death in a dose-dependent manner. The IC50 of Bryonia dioica aqueous extract was estimated to be approximately 15, 63µg/ml. This was accompanied by induction of apoptosis, activation of caspase-3 and -9, cleavage of PARP and loss of mitochondria membrane potential. Furthermore, the phytochemical screening of roots of Bryonia dioica showed the presence of various bioactive such as polyphenols, sterols and triterpenes, alkaloids, c-heterosides, carbohydrates and saponins. CONCLUSION: The aqueous extract of Bryonia dioica induces apoptosis in the Burkitt's lymphoma BL41 cell lines via the mitochondrial pathway. The flavonoids, sterols and triterpens detected could be responsible for the cytotoxic and apoptogenic activities of the aqueous extract of Bryonia dioica. These findings suggest that Bryonia dioica could be considered as a promising source for developing novel therapeutics against Burkitt's lymphoma.