Radio-protective Potentials of Methanolic/Aqueous Extract of Adasonia digitata and Cochorous olitorious Leaf Plant on Gamma Irradiated Male Wistar Rats

It is no longer news that technology is eating deep as a cankerworm in the heart of human and it is pertinent to know that 90% of the world-used technological gadget are fully equipped with radiation emitting software, which upon human exposure to, generating free radicals-induce disease and several disorders such as hemorrhage induced anaemia, cancer, ischemia reperfusion diseases, diabetes, atherosclerosis and several others (Haliwell, 2000). Hence the needs to prevent, ameliorate, attenuate and cure the effects of radiation generating disorders. Some groups of rat were exposed to gamma radiation of 6Grey, generating free radicals and inducing several diseases and disorders. A. digitata and C.olitorious has been established to poses significant (p<0.05) amounts of antioxidant phytochemicals (inducers of endogenous antioxidant enzymes) such as Saponin(16.59±1.85 and 22.12±0.24),Tannins(311.98±0.01 and 287.07±0.16), Polyphenols(170.90±0.68 and 330.07±0.32),Alkaloids(81.56±0.56 and 68.65±2.05) and flavonoids(25.38±2.88 and 157.38±0.38) which is suggestive of the free radical scavenging potentials of the two plants extracts. The administration of the plant extract to rats exposed to radiation was able to attenuate and prevent the disorders, implicating the plant extracts to be radioprotective and antioxidative in potentials. The safety evaluation analysis was examined by measuring the serum ALT, AST and ALP level which was not significantly (p<0.05) different when compared to the normal control, establishing the Hepatoprotective potential of the plant extracts. Keywords: Antioxidative, ameliorate, Free Radicals, Radiation, Hepatoprotective, Radioprotectiv

Pharmacognostical, Phytochemical and Anticancer Activity of the Leaves of Asparagus Racemosus Willd., (Liliaceae)

AIM:The main aim of the present work is to study the anticancer activity of the leaves of Asparagus racemosus Willd.,OBJECTIVES:To standardize the leaves of Asparagus racemosus Willd., by carrying out the pharmacognostical and phytochemical studies. To evaluate the invitro anticancer activity of various extracts To evaluate the invivo anticancer activity Isolation and identification of Rutin SUMMARY AND CONCLUSION:Cancer is one of the leading causes of death worldwide. Currently available allopathic drugs for treating cancer causes number of side effects hence, people are now looking towards the herbal medicine. This paved a vital necessity for finding natural anticancer drug from herbal source. Asparagus racemosus Willd., is one such plant which is traditionally used in the treatment of cancer was selected for the present study. The literature survey showed only scrappy information on the leaves of this plant. With this scanty of information on the leaves, consistent expectation of unexplored phytochemical profile and pharmacological efficacy forms the rationale for the study.Pharmacognostical studies A perusal of literature showed paucity of pharmacognostical information on the leaves of this plant. Hence, it was carried out and reported for the first time. In pharmacognostical studies macroscopy, microscopy, determination of physicochemical constants, analysis of inorganic elements, heavy metals and pesticide residue of the leaves were carried out. Macroscopical study showed that the leaves are pine needle (phylloclades) shaped, sweet and bitter taste and dark green in colour. The various distinguishing features of leaves observed through anatomical studies were, Phyllodades 3-4 angled with lateral projections Radially oblong epidermal cells with prominent cuticle Circular chlorophyllous palisade cells Vascular strands with angular xylem and thick mass of phloem elementsThe microscopical analysis of powder showed the presence of lignified fibres, epidermis with palisade cells and stomata. Various physicochemical constants such as ash values, extractive values, loss on drying, crude fibre content, swelling index and foaming index were carried out. These values will help in confirming the identity and purity of the plant. Any significant deviation in the percentage of any parameters reported in this work may indicate adulteration or substitution in the drug. Qualitative estimation of inorganic elements, quantitative estimation of heavy metals and pesticide residue were carried out and it showed only trace amount of heavy metals (within the limits) and absence of pesticide residue. These pharmacognostical details observed from the present study might offer reliable clues for the correct identification of the leaves of this plant in crude as well as fragmentary form and also ensures its differentiation from its substitutes and adulterants. This is first report on the pharmacognostical standardization on the leaves of Asparagus racemosus Willd.,Phytochemical studies Phytochemical evaluation deals with chemical analysis of the extracts used for pharmacological screening. The successive solvent extraction was carried out with solvents like n-Hexane, chloroform, ethyl acetate and ethanol. Chloroform extract showed more percentage yield when compared to other extracts. Qualitative preliminary phytochemical analysis was aided in identifying the phytoconstituents present in different extracts. Quantitative estimation of flavanoid, tannin and phenolic content were carried out, for the extracts. Fluorescence analysis was carried out, to detect the fluorescent chromophores present in the powdered drug as well as in the extracts. No fluorescence was observed in powder and the extracts. Thin layer chromatography for the extracts was performed to identify the single or mixture of constituents in the extract. High Performance Thin Layer Chromatography- Finger print profile was carried out to detect the number of constituents present in the ethyl acetate extract. Invitro studies:The therapeutically active extract to carry out the invivo anticancer activity was selected based on invitro anticancer activity. The chloroform, ethyl acetate and ethanol extracts were subjected to invitro anticancer studies using HeLa cells line by MTT assay. Chloroform and ethyl acetate extracts showed significant anticancer activity by MTT assay and these two extracts were selected for invivo anticancer studies.Acute toxicity studies:Acute toxicity study was carried out for chloroform and ethyl acetate extracts according to OECD guidelines 423. The extracts are non-toxic up to 2000mg/kg body weight indicating the safety of the extracts.Invivo anticancer studies:Invivo anticancer activity of chloroform and ethyl acetate extracts were carried out on Ehrlich’s Ascites Carcinoma (EAC) bearing mice. The ethyl acetate extract showed significant anticancer activity at the dose of 400mg/kg body weight when compared to chloroform extract and the effects were comparable with the standard drug. Since, rutin was found to possess anticancer activity, an attempt was made to isolate rutin by partition separation method. The isolated compound was subjected to melting point, chemical test, TLC and IR spectroscopic studies. From the above mentioned studies, it can be concluded that the pharmacognostical standards generated for the leaves will be useful for the proper identification of the plant. With the support of phytochemical and invitro cytotoxic activity the chloroform and ethyl acetate extracts were selected and subjected to invivo anticancer activity. The ethyl acetate extract at the dose level of 400mg/kg showed significant anticancer activity. Further studies are focused on detailed spectral analysis of isolated rutin and isolation of other phytoconstituents which is responsible for anticancer activity of the leaves

Evaluation of ASVERADO For its Anti-Neoplastic Activity Against 7,12- Dimethyl benz[a]anthracene (DMBA) Induced Mammary Gland Carcinoma in Female Wistar Rats

AIM AND SCOPE OF WORK: Cancer, being a cause of death for major fraction of population worldwide, is one of the most studied diseases and is being investigated for the development of new technologies and more accurate therapies. Still the currently available therapies for cancer have many lacunae which affect the patient‟s health severely in the form of side effects. The natural drugs obtained from the medicinal plants provide a better alternative to fight against this devastating disease. Breast cancer and cancer related diseases have been treated using surgery, chemotherapy, and radiation therapy, or a combination of these. Despite these therapeutic options, cancer remains associated with high mortality. Traditional medicine which involves the use of herbs has been used to treat various types of cancer and this has been found to be effective with minimal or no side effects. It was also highlighted in introductory part the need of alternative system of herbal medicine for treating various ailments. The review of literature shows many uses and different studies for cancer on Avocado, Aloe vera and Ashwagandha. This research was aimed to evaluate the both in-vitro studies using Breast cancer cell line (MCF-7) & in-vivo studies based on the ethanolic extract of ASVERADO for its anti-neoplasttic activity against 7,12-dimethylbenzeneanthracene (DMBA) induced Mammary gland carcinoma in female Wistar rats. So that it may serve clinically for the management of cancer. SUMMARY: The present study was conducted for evaluation of ameliorating potential in terms of anticancerous and antioxidative properties of herbal ethanolic extract of ASVERADO from fruit of Persea Americana Mill, leaves of Aloe vera (L.) Burm.f., & Root of Withania Somnifera on DMBA induced mammary tumorigenesis in Wistar rats. The preliminary phytochemical studies on ASVERADO discovered the presence of various phytoconstituents such as alkaloid, carbohydrates, glycosides, steroid, proteins, flavonoids and saponin. This research was aimed to evaluate the both in-vitro studies using Breast cancer cell line (MCF-7) & in-vivo studies based on the ethanolic extract of ASVERADO for its anti-neoplasttic activity against 7,12-dimethylbenzeneanthracene (DMBA) induced Mammary gland carcinoma in female Wistar rats. The biochemical parameters like Blood Sugar level, Hb count,Albumine, RBC count,PCV, MCV, MCH,MCHC,Total count, Polymorph, Lymphocytes,Eosinophils,Globulin and Total Protein Binding values showed increase in the ASVERADO treated rats when to compared to DMBA treated rats. The antioxidants defense in the mammary gland tissues were estimated in terms of SOD, CAT, LPO and ASVERDO increased the antioxidant levels at respective dose leading to reduce oxidative stress. This clearly indicates the potential of the extract to delay the generation of free radicals that cause carcinogenesis. The histopathology of DMBA treated rats showed increased in tumor cells. Whereas the control and ASVERADO treated rats showed normal level of tumor cells. CONCLUSION: The present study demonstrated that DMBA induced mammary gland carcinoma in Wistar rats. Ethanolic extract of ASVERADO from fruit of Persea Americana Mill, leaves of Aloe vera (L.) Burm.f., & Root of Withania Somnifera which helps in suppressing tumor cells. The anti-oxidant has potential of delaying the generation of free radicals that cause carcinogenesis. Further studies are expected on the isolated components of the extract in order to understand the exact mechanism of its action and also studies at cellular level changes by more sophisticated methods for investigation

Chemical Radioprotectors

Protection of biological systems against radiation damage is of paramount importance during accidental and unavoidable exposure to radiation. Several physico-chemical and biological factors collectively contribute to the damage caused by radiation and are, therefore, targets for developing radioprotectors. Work on the development of chemicals capable of protecting biological systemsfrom radiation damage was initiated nearly six decades ago with cysteine being the first molecule to be reported. Chemicals capable of scavenging free radicals, inducing oxygen depletion,antioxidants and modulators of immune response have been some of the radioprotectors extensively investigated with limited success. Mechanism of action of some chemical radioprotectors and their combinations have been elucidated, while further understanding is required in many instances. The present review elaborates on structure-activity relationship of some of the chemical radioprotectors, their evaluation, and assessment, limitation, and future prospects

Protective Effects of Hydroalcoholic Extract of Boerhaavia Diffusa Linn Against Cisplatin Induced Nephrotoxicity in Rats

The present studies, the cisplatin treated animals showed a significant increase in blood urea, blood urea nitrogen and serum creatinine. As shown in [Table no:4] serum creatinine, Blood urea nitrogen (BUN), and blood urea levels were significantly higher after 72 h respectively, after administration of single dose of cisplatin when compared to the control group. The pre-treatment with Hydro alcoholic extract of Boerhaavia diffusa (HAEBD) p.o. significantly (P < 0.01) lowered the elevated serum urea creatinine, and Blood urea nitrogen (BUN). When compared to the cisplatin group. The pre-treatment with silymarin showed a marked decrease in concentrations of blood urea, serum creatinine, Blood urea nitrogen and alkaline phosphatise, it was shown that cisplatin treatment induced renal damage and pretreatment with hydro alcoholic extract of Boerhaavia diffusa (HAEBD) provided protective effect against this cisplatin-induced nephrotoxicity. However, before concluding a potential usefulness of hydro alcoholic extract of Boerhaavia diffusa (HAEBD) as adjunct to the cisplatin therapy, further clinical investigation is needed

The Determinants of Nutritional Risk in Paediatric Cancer

The five-year survival rates of paediatric cancer patients have improved considerably in the last 40 years with the implementation of more intensive and progressive treatments. Consequently attention is shifting to the reduction of treatment-related sequelae during and after the completion of therapy. Malnutrition and vitamin D inadequacy are a major concern as they are thought to increase the risk of short- and long-term complications in this population. Furthermore, emerging evidence has found a protective role of antioxidants and docosahexanoic acid (DHA) and eicosapentaenoic acid (EPA) against chronic conditions, including cardiovascular disease and cancer, which are common long-term complications in survivors of paediatric cancer. Therefore, this thesis aimed to investigate the nutritional status (NS), vitamin D, antioxidants and oxidative stress levels, as well as DHA and EPA levels of paediatric cancer patients. Potential factors that may contribute to the development of malnutrition in this population were also investigated. A prospective cohort-study of SE Scottish children aged 95th). Vitamin D status was defined by the Endocrine Society Clinical Practice Guidelines (2011); inadequacy (<50nmol/L). Eighty-two patients [median(IQR) age 3.9(1.9-8.8) years; 56% males)] were recruited. At diagnosis, the prevalence of undernutrition was 13%, overweight 7% and obesity 15%. TSF identified the highest prevalence of undernutrition (15%) and the lowest of obesity (1%). BMI [p<0.001; 95% CI (1.31-3.47)] and FM (BIA) [p<0.05; 95% CI (0.006-0.08)] significantly increased after 3 months of treatment, whilst FFM (BIA) [p<0.05; 95% CI (-0.78-(-0.01)] significantly decreased during the first three months and these patterns remained until the end of the study. High-treatment risk significantly contributed to undernutrition during the first three months of treatment [p=0.04; 95% CI (-16.8-(-0.4)] and solid tumours had the highest prevalence of undernutrition [BMI (17%)]. Vitamin D inadequacy was highly prevalent (64%; 42/65) at both baseline and during treatment (33-50%) and those children who were not supplemented had the lowest vitamin D levels at every stage with median(IQR) levels ranging from 32.0(21.0-46.5)nmol/L to 45.0(28.0-64.5)nmol/L. Paediatric cancer patients had high levels of oxidative stress and low levels of DHA and EPA, especially at baseline. Antioxidant status remained steady at 6 months, however antioxidant capacity increased slightly. Finally, antioxidant levels, antioxidant capacity, oxidative stress and EPA and DHA did not statistically differ between children receiving nutritional support and those who were not. Arm anthropometry (or BIA) alongside appropriate nutritional supplementation should be implemented in clinical practice due to the high risk of malnutrition (undernutrition and obesity), the changes in body composition (increase in fat mass and reduction in lean mass) and vitamin D inadequacy, as well as the low levels of EPA and DHA seen in this paediatric cancer cohort.sub_dnbsunpub2078_ethesesunpu

Prevalence of the Use of Herbal Medicines among Patients with Cancer: A Systematic Review and Meta-Analysis

Background: Although herbal medicines are used by patients with cancer in multiple oncology care settings, the magnitude of herbal medicine use in this context remains unclear. )e purpose of this review was to establish the prevalence of herbal medicine use among patients with cancer, across various geographical settings and patient characteristics (age and gender categories). Methods: Electronic databases that were searched for data published, from January 2000 to January 2020, were Medline (PubMed), Google Scholar, Embase, and African Index Medicus. Eligible studies reporting prevalence estimates of herbal medicine use amongst cancer patients were pooled using random-effects meta-analyses. Studies were grouped by World Bank region and income groups. Subgroup and meta regression analyses were performed to explore source of heterogeneity. Results: In total, 155 studies with data for 809,065 participants (53.95% female) met the inclusion criteria. Overall, the pooled prevalence of the use of herbal medicine among patients with cancer was 22% (95% confidence interval (CI): 18%–25%), with the highest prevalence estimates for Africa (40%, 95% CI: 23%–58%) and Asia (28%, 95% CI: 21%–35%). )e pooled prevalence estimate was higher across low- and middle-income countries (32%, 95% CI: 23%–42%) and lower across high-income countries (17%, 95% CI: 14%–21%). Higher pooled prevalence estimates were found for adult patients with cancer (22%, 95% CI: 19%–26%) compared with children with cancer (18%, 95% CI: 11%–27%) and for female patients (27%, 95% CI: 19%–35%) compared with males (17%, 95% CI: 1%–47%). Conclusion: Herbal medicine is used by a large percentage of patients with cancer use. The findings of this review highlight the need for herbal medicine to be integrated in cancer care

In vivo toxicological evaluation of peptide conjugated gold nanoparticles for potential application in colorectal cancer diagnosis

Colorectal cancer (CRC) is among the leading cause of cancer-related deaths in South Africa and worldwide. Efforts are being made at finding improved diagnostic tools, as early detection (before metastasis) is a major factor in CRC treatment. Colonoscopy is the most reliable detection method, but is a specialised and expensive procedure, which is invasive, not readily available and not patient-friendly. There is a risk of developing interval cancers, as colonoscopies are performed every 10 years after the age of 40. The development of non-invasive, cost efficient and readily available diagnostic tools to CRC, which can be performed at more regular intervals, using tumour-targeting molecular imaging agents, is of urgent attention. Gold nanoparticles (AuNPs) possess several physicochemical properties, including ease of synthesis, biocompatibility, and the ability to be conjugated by ligands or biomolecules such as polyethylene glycol (PEG) and peptides for improved stability, tissue targeting and selectivity. These factors potentiate the role in biomedical applications, including cancer theranostics. Conjugation of AuNPs with a targeting molecule (e.g. antibody or peptide) is directed against cancer cell receptors. The peptides, p.C, p.L, and p.14, bind to CRC cells in vitro. Conjugation of AuNPs with these peptides should be investigated for CRC diagnosis in vivo, as it is hypothesised to allow examinations at shorter intervals through imaging techniques. This could reduce the risk of interval cancers, but before developing this novel tool, in vivo toxicity evaluations are essential. This study was therefore aimed at investigating the short- and long-term toxicological effects of a single intravenous injection of peptides (p.C, p.L, and p.14) conjugated to AuNPs in a healthy rat model. Citrate-capped AuNPs were synthesised by the citrate-reduction method, and conjugated with each peptide (biotinylated) using a combination of PEG (99% PEG-OH and 1% PEG-biotin) as a stabilising agent and linker, via biotin-streptavidin interaction. Healthy male Wistar rats were intravenously injected with 14 nm citrate-AuNPs, PEG-, p.C-PEG, p.L-PEG, and p.14-PEG-AuNPs (100 μg/kg body weight), and the control rats were injected with phosphate buffered saline. The animals were monitored for behavioural, physiological, biochemical, haematological and histological changes, as well as inflammatory responses. Phase 1 rats were sacrificed 2 weeks post-injection to determine the immediate or acute toxicity of the AuNPs, while phase 2 animals were sacrificed 12 weeks post-injection, to investigate the delayed or persistence toxicity of the AuNPs. Results revealed no significant toxicities with the citrate, PEG-, p.C-PEG and p.14-PEG-AuNPs over 12 weeks post-exposure, as evidenced by biochemical assays such as serum marker enzymes, liver and kidney function markers, and cholestatic indicators; haematological parameters; oxidative stress markers; and histopathological examinations. P.L-PEG-AuNPs, however, caused significant toxicity (p<0.05) to rats, as evidenced by increased relative liver weight, increased malondialdehyde levels, and total white blood cell counts 2 weeks post-exposure when compared to the control group. This was, however, reversed during the 12 weeks post-exposure. Further, there were no evidence of inflammatory responses, using pro-inflammatory markers including phospho interleukin 18 (IL-18) and interferon-γ (IFN-γ), as indicated by immunohistochemical staining of the liver, spleen, kidney and colon of rats 2 weeks post-injection of AuNPs. Citrate, PEG-, p.C-PEG, and p.14-PEG-AuNPs did not induce immediate, acute or persistent toxicity, while p.L-PEG-AuNPs induced a transient acute toxicity. It can be concluded that 14 nm spherical citrate-AuNPs at 100 μg/kg body weight is a good candidate for biomedical applications, and as a suitable carrier for diagnostic and/or therapeutic molecules. Combination of 99% PEG-OH and 1% PEG-biotin is an appropriate option for stabilising AuNPs in biological environment, and conjugating secondary diagnostic or therapeutic biomolecules or agents to citrate-capped AuNPs. Peptide-conjugated AuNPs are suitable for the development into a diagnostic tool for CRC in vivo

In vivo toxicological evaluation of peptide conjugated gold nanoparticles for potential application in colorectal cancer diagnosis

Colorectal cancer (CRC) is among the leading cause of cancer-related deaths in South Africa and worldwide. Efforts are being made at finding improved diagnostic tools, as early detection (before metastasis) is a major factor in CRC treatment. Colonoscopy is the most reliable detection method, but is a specialised and expensive procedure, which is invasive, not readily available and not patient-friendly. There is a risk of developing interval cancers, as colonoscopies are performed every 10 years after the age of 40. The development of non-invasive, cost efficient and readily available diagnostic tools to CRC, which can be performed at more regular intervals, using tumour-targeting molecular imaging agents, is of urgent attention. Gold nanoparticles (AuNPs) possess several physicochemical properties, including ease of synthesis, biocompatibility, and the ability to be conjugated by ligands or biomolecules such as polyethylene glycol (PEG) and peptides for improved stability, tissue targeting and selectivity. These factors potentiate the role in biomedical applications, including cancer theranostics. Conjugation of AuNPs with a targeting molecule (e.g. antibody or peptide) is directed against cancer cell receptors. The peptides, p.C, p.L, and p.14, bind to CRC cells in vitro. Conjugation of AuNPs with these peptides should be investigated for CRC diagnosis in vivo, as it is hypothesised to allow examinations at shorter intervals through imaging techniques. This could reduce the risk of interval cancers, but before developing this novel tool, in vivo toxicity evaluations are essential. This study was therefore aimed at investigating the short- and long-term toxicological effects of a single intravenous injection of peptides (p.C, p.L, and p.14) conjugated to AuNPs in a healthy rat model. Citrate-capped AuNPs were synthesised by the citrate-reduction method, and conjugated with each peptide (biotinylated) using a combination of PEG (99% PEG-OH and 1% PEG-biotin) as a stabilising agent and linker, via biotin-streptavidin interaction. Healthy male Wistar rats were intravenously injected with 14 nm citrate-AuNPs, PEG-, p.C-PEG, p.L-PEG, and p.14-PEG-AuNPs (100 μg/kg body weight), and the control rats were injected with phosphate buffered saline. The animals were monitored for behavioural, physiological, biochemical, haematological and histological changes, as well as inflammatory responses. Phase 1 rats were sacrificed 2 weeks post-injection to determine the immediate or acute toxicity of the AuNPs, while phase 2 animals were sacrificed 12 weeks post-injection, to investigate the delayed or persistence toxicity of the AuNPs. Results revealed no significant toxicities with the citrate, PEG-, p.C-PEG and p.14-PEG-AuNPs over 12 weeks post-exposure, as evidenced by biochemical assays such as serum marker enzymes, liver and kidney function markers, and cholestatic indicators; haematological parameters; oxidative stress markers; and histopathological examinations. P.L-PEG-AuNPs, however, caused significant toxicity (p<0.05) to rats, as evidenced by increased relative liver weight, increased malondialdehyde levels, and total white blood cell counts 2 weeks post-exposure when compared to the control group. This was, however, reversed during the 12 weeks post-exposure. Further, there were no evidence of inflammatory responses, using pro-inflammatory markers including phospho interleukin 18 (IL-18) and interferon-γ (IFN-γ), as indicated by immunohistochemical staining of the liver, spleen, kidney and colon of rats 2 weeks post-injection of AuNPs. Citrate, PEG-, p.C-PEG, and p.14-PEG-AuNPs did not induce immediate, acute or persistent toxicity, while p.L-PEG-AuNPs induced a transient acute toxicity. It can be concluded that 14 nm spherical citrate-AuNPs at 100 μg/kg body weight is a good candidate for biomedical applications, and as a suitable carrier for diagnostic and/or therapeutic molecules. Combination of 99% PEG-OH and 1% PEG-biotin is an appropriate option for stabilising AuNPs in biological environment, and conjugating secondary diagnostic or therapeutic biomolecules or agents to citrate-capped AuNPs. Peptide-conjugated AuNPs are suitable for the development into a diagnostic tool for CRC in vivo