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Background: Viral hemorrhagic fevers (VHF) refers to a group of febrile illnesses caused by different viruses that result in high mortality in animals and humans. Many risk factors like increased human-animal interactions, climate change, increased mobility of people and limited diagnostic facility have contributed to the rapid spread of VHF. Materials: The history of VHFs in the Saudi Arabian Peninsula has been documented since the 19th century, in which many outbreaks have been reported from the southwestern region of Saudi Arabia. Despite presence of regional network of experts and technical organizations, which expedite support and respond during outbreaks, there are some more challenges that need to be addressed immediately. Gaps in funding, exhaustive and inclusive response plans and improved surveillance systems are some areas of concern in the region which can be dealt productively. This review primarily focusses on the hem- orrhagic fevers that are caused by three most common viruses namely, the Alkhurma hemorrhagic fever virus, Rift valley fever virus, and Dengue fever virus. Conclusion: In summary, effective vector control, health education, possible use of vaccine and concerted synchronized efforts between different government organizations and private research institutions will help in planning effective out- break-prevention and response strategies in future. Keywords: Viral fever; hemorrhagic fever (VHF); Saudi Arabia; challenges; management; future considerations.

Rocket (Eruca sativa) is a low-calorie leafy vegetable of the family Brassicaceae under the genera Eruca mostly consumed raw in salads. It has been used since ancient times from food to medicine and cosmetics without any knowledge of the mechanism or the targets involved. However, presently, the production and cultivation of rocket have significantly increased owing to its different biological effects. Erucin and Sulforaphane are the most commonly studied isothiocyanates obtained from the plant parts of Eruca sativa. Over time, with continuous usage of conventional and synthetic drugs, the drug resistant and off-target toxicities rapidly increase, which necessitates for alternative medicine with increased specificity and minimal detrimental effects. It is interesting to note that many previous studies have reported the antimicrobial impact of E. sativa against the pathogenic bacterial species like Escherichia coli, Staphylococcus aureus, Salmonella typhimurium, etc. Moreover, Erucin obtained from E. sativa has shown significant inhibitory and protective effect against different human cancer cell lines and xenograft animal models. The present review gives a brief overview of the antimicrobial, neuroprotective and anticancer effects of the various plant parts of E. sativa and the most bioactive isothiocyanates. It is exciting to note that epigenetic modulation of gene expression has also been reported in some studies which could be a new direction of research on the path of naturopathy.

In this study, we investigated the inhibitory effects of m-coumaric acid on the glycosylation of proteins in the retinas of diabetic rats. Male rats were divided into two main groups, Group I (normal control) and Group II (diabetic); Group II was further divided into four subgroups: Group IIa (diabetic control), Group IIb (diabetic rats were given m-coumaric acid orally [150 mg/kg, body weight (bw)/day]), Group IIc (diabetic rats were given HCA m-coumaric acid orally [300 mg/kg bw/day]), and Group IId (diabetic rats were given insulin [10 units/kg bw/day]) as a positive control). The treatment lasted for six weeks, and the data obtained suggested that m-coumaric acid reduced glucose and glycated hemoglobin levels, which further decreased the formation of glucose-derived advanced glycation end products. Hence, it protected the tissues from the detrimental effects of hyperglycemia and enhanced antioxidant activity. In conclusion, m-coumaric acid could be a potential candidate to prevent the onset and progression of retinopathy in diabetic patients.

Human hepatocellular carcinoma (HCC) is the most common and recurrent type of primary adult liver cancer without any effective therapy. Plant-derived compounds acting as anticancer agents can induce apoptosis by targeting several signaling pathways. Strigolactone (SL) is a novel class of phytohormone, whose analogues have been reported to possess anticancer properties on a panel of human cancer cell lines through inducing cell cycle arrest, destabilizing microtubular integrity, reducing damaged in the DNA repair machinery, and inducing apoptosis. In our previous study, we reported that a novel SL analogue, TIT3, reduces HepG2 cell proliferation, inhibits cell migration, and induces apoptosis. To decipher the mechanisms of TIT3-induced anticancer activity in HepG2, we performed RNA sequencing and the differential expression of genes was analyzed using different tools. RNA-Seq data showed that the genes responsible for microtubule organization such as TUBB, BUB1B, TUBG2, TUBGCP6, TPX2, and MAP7 were significantly downregulated. Several epigenetic modulators such as UHRF1, HDAC7, and DNMT1 were also considerably downregulated, and this effect was associated with significant upregulation of various proapoptotic genes including CASP3, TNF-α, CASP7, and CDKN1A (p21). Likewise, damaged DNA repair genes such as RAD51, RAD52, and DDB2 were also significantly downregulated. This study indicates that TIT3-induced antiproliferative and proapoptotic activities on HCC cells could involve several signaling pathways. Our results suggest that TIT3 might be a promising drug to treat HCC.

Negligence of oral hygiene is one of the chief causes of oral complications affecting human health worldwide, regardless of demographics, consequently contributing to the increasing global death rate. Inadequate oral hygiene is linked with numerous diseases and oral cavity is the gateway to many pathogens, which may lead to death by inviting life-threatening ailments such as antimicrobial drug resistance and cancer. About 70% of oral cancers are preceded by the onset of precancerous oral lesions. According to WHO, oral diseases occupy fourth position in terms of treatment expense, which subsequently adds the burden on the developing countries by investing resources for the upliftment of healthcare systems in maintaining oral hygiene. There is an urgent need to find out a solution to prevent the oral diseases, which is accessible and equally affordable by each individual. Salvadora persica is a traditional herb, which gained importance in the modern medicine, due to its documented oral treatment, since time immemorial, and contemporary research evidences proving its therapeutic potential. S. persica has varied pharmacological properties such as antimicrobial, reducing dental plaque, and anti-inflammatory, anti-carcinogenic, and anticancer activities. S. persica has vital phytochemicals such as saponins, tannins, flavonoids, terpenoids, and the most prominent benzyl isothiocyanate. In this communication, we have discussed the role of S. persica in maintaining the oral health and its medicinal efficacy towards treatment of various ailments.

Medicinal plants were the only source of therapeutic treatment in the primary healthcare systems in ancient times, before the discovery of modern medicinal practices. However, in the past two decades, herbal products/medicinal herbs encompassing potential bioactive compounds have caught attention of the researchers globally. Alike other prominent herbs, Anethum graveolens (dill) have been cultivated since time immemorial for medicinal and culinary purposes, dating back to the Greek and Egyptian civilizations. The objective of this chapter is to provide comprehensive understanding of the extensive research related to A. graveolens and its active compounds. It focuses on the therapeutic effects of A. graveolens as exhibited by various in vivo and in vitro studies, confirming its anticancer, antimicrobial, hypolipidemic, and hypoglycemic properties. Moreover, the randomized clinical trials and molecular interaction studies performed with the active component of A. graveolens are also discussed, highlighting its efficacy as a safe complementary alternative medicine aiding the management of cardiovascular diseases, diabetes, and cancer.

Thymoquinone (TQ), a natural anticancer agent exerts cytotoxic effects on several tumors by targeting multiple pathways, including apoptosis. Difluoromethylornithine (DFMO), an irreversible inhibitor of the ornithine decarboxylase (ODC) enzyme, has shown promising inhibitory activities in many cancers including leukemia by decreasing the biosynthesis of the intracellular polyamines. The present study aimed to investigate the combinatorial cytotoxic effects of TQ and DFMO on human acute T lymphoblastic leukemia Jurkat cells and to determine the underlying mechanisms. Here, we show that the combination of DFMO and TQ significantly reduced cell viability and resulted in significant synergistic effects on apoptosis when compared to either DFMO or TQ alone. RNA-sequencing showed that many key epigenetic players including Ubiquitin-like containing PHD and Ring finger 1 (UHRF1) and its 2 partners DNA methyltransferase 1 (DNMT1) and histone deacetylase 1 (HDAC1) were down-regulated in DFMO-treated Jurkat cells. The combination of DFMO and TQ dramatically decreased the expression of UHRF1, DNMT1 and HDAC1 genes compared to either DFMO or TQ alone. UHRF1 knockdown led to a decrease in Jurkat cell viability. In conclusion, these results suggest that the combination of DFMO and TQ could be a promising new strategy for the treatment of human acute T lymphoblastic leukemia by targeting the epigenetic code.

The use of herbal formulations has gained momentum in recent past with many people using natural product-based substances to stay away from dental health issues. In the present study, the patient is treated by using herbal mouthwash containing Baccharis dracunculifolia. Figure 7.1 displays the result of treatment accompanied by herbal mouthwash. This study was carried out under the NTR Health University.

Deterioration of oral health and tooth deformities are progressive and ultimately lead to tooth loss and subsequently may result in increased mortality rates. Since there is a strong relation between oral health and general health, the diminishing oral health could progressively lead to various ailments. Although there are different reasons for the cause of a particular disease, there is strong evidence that it could be significantly related to lack of proper oral hygiene. The dental caries due to loss of oral health may lead to different disorders or diseases such as cardiovascular and respiratory disorders, stroke, dementia, chronic renal failure, and stomach ulcers. The use of poor dietary practices, tobacco, unhygienic conditions, and negligence of initial dental problems are the major reasons for the progression of dental diseases. Diet could be a major deciding factor in the decline or improvement of oral health. Hence, the emergence of various diseases and deformities due to loss of oral health are remarkable, and they have serious impact on overall health of an individual.

The use of traditional medicine used to be one of the primary sources of treatment for various diseases around the world in the past. Although the usage was restricted to rural areas and low economy areas, the urban population has also begun to express their interest in the consumption of products manufactured from natural sources. The success of the traditional medicine depends on the expertise of the traditional healer. In the recent past, the use of herbal medicine and natural product-based drugs has stepped up with reports being published with their multiple benefits. Use of complementary medicine for overcoming the oral diseases is found to be successful based on its mode of application and usage on the patient. Among the traditional oral remedies, the most imperative remedy is “oil pulling technique” followed by use of some traditional medicinal plants. Oil pulling technique removes the toxins and bacteria by trapping them in the oil. Moreover, different parts of medicinal plants are used for treating the oral diseases at the primary levels. Olea europaea leaf decoction is used to combat mouth and gum diseases through gargling.

Natural product-based drugs have become trendsetters in the field of medicine as alternative or complementary remedy due to the admirable and predominant advantages they possess in comparison to the synthetic counterparts. Although many reports have been published regarding the biological activities of the natural products, very few reach the stages of clinical trials and get approved. There are various dental formulations available in the market currently, which are used according to the patient’s requirement and disease severity for overcoming oral health deformities. The data presented here lists some medicinal plants used in dentistry that have been approved by various clinical trial registries around the world and their specifications and applications.

Medicinal plants have played a dominant and extensive role in the discovery of less expensive, more potent and reliable source of drugs against oral diseases. The continuous use of synthetic chemical substances in dentistry has shown off-target toxicities; this has necessitated the discovery of some alternative medicine with least side effects and high efficiency. Emergence of resistance towards the present antibiotics and the immunodeficiency has prompted researchers to discover novel drug leads against numerous diseases. Broad biological effects such as anti-inflammatory, antimicrobial, analgesic, antifungal and antioxidant activity has been demonstrated by herbal medicines used in the treatment of oral diseases. Plants are used in the maintenance of oral hygiene by various means, which includes nourishing oral health, combating and prevention of oral diseases. Hence, the use of medicinal herbs for improvement of oral health and dental hygiene is a marked advantage of these herbal formulations.

Oral hygiene is an important aspect for the well-being of an individual which could be achieved by maintaining a healthy lifestyle. As oral cavity is an open gateway for various microorganisms, multiple complications can occur due to entry of pathogenic microbes through mouth and accumulation in the oral cavity resulting in deterioration of teeth gradually. The saliva produced in the mouth contains various enzymes which possess antibacterial activity. Oral health loss may lead to one or many of the complications such as oral infection, oral cancer, radiating pain, periodontal diseases, tooth loss, and tooth decay. Therefore, maintenance of proper oral health is fundamental for “adding years to life and life to years” any negligence may cause severe complications in the long run.

Natural polyamines such as putrescine, spermidine, and spermine are crucial in the cell proliferation and maintenance in all the eukaryotes. However, the requirement of polyamines in tumor cells is stepped up to maintain tumorigenicity. Many synthetic polyamine analogues have been designed recently to target the polyamine metabolism in tumors to induce apoptosis. N4-Erucoyl spermidine (designed as N4-Eru), a novel acylspermidine derivative, has been shown to exert selective inhibitory effects on both hematological and solid tumors, but its mechanisms of action are unknown. In this study, RNA sequencing was performed to investigate the anticancer mechanisms of N4-Eru-treated T-cell acute lymphoblastic leukemia (ALL) cell line (Jurkat cells), and gene expression was examined through different tools. We could show that many key oncogenes including NDRG1, CACNA1G, TGFBR2, NOTCH1,2,3, UHRF1, DNMT1,3, HDAC1,3, KDM3A, KDM4B, KDM4C, FOS, and SATB1 were downregulated, whereas several tumor suppressor genes such as CDKN2AIPNL, KISS1, DDIT3, TP53I13, PPARG, FOXP1 were upregulated. Data obtained through RNA-Seq further showed that N4-Eru inhibited the NOTCH/Wnt/JAK-STAT axis. This study also indicated that N4-Eru-induced apoptosis could involve several key signaling pathways in cancer. Altogether, our results suggest that N4-Eru is a promising drug to treat ALL.

Natural polyamines such as putrescine, spermidine, and spermine are crucial in the cell proliferation and maintenance in all the eukaryotes. However, the requirement of polyamines in tumor cells is stepped up to maintain tumorigenicity. Many synthetic polyamine analogues have been designed recently to target the polyamine metabolism in tumors to induce apoptosis. N 4 -Erucoyl spermidine (designed as N 4 -Eru), a novel acylspermidine derivative, has been shown to exert selective inhibitory effects on both hematological and solid tumors, but its mechanisms of action are unknown. In this study, RNA sequencing was performed to investigate the anticancer mechanisms of N 4 -Eru-treated T-cell acute lymphoblastic leukemia (ALL) cell line (Jurkat cells), and gene expression was examined through different tools. We could show that many key oncogenes including NDRG1, CACNA1G, TGFBR2, NOTCH1,2,3, UHRF1, DNMT1,3, HDAC1,3, KDM3A, KDM4B, KDM4C, FOS , and SATB1 were downregulated, whereas several tumor suppressor genes such as CDKN2AIPNL, KISS1, DDIT3, TP53I13, PPARG, FOXP1 were upregulated. Data obtained through RNA-Seq further showed that N 4 -Eru inhibited the NOTCH/Wnt/JAK-STAT axis. This study also indicated that N 4 -Eru-induced apoptosis could involve several key signaling pathways in cancer. Altogether, our results suggest that N 4 -Eru is a promising drug to treat ALL.

Chemotherapy shows some promising results in the inhibition of cancer, but resistance to chemotherapy and its severe side effects may occur in due course, resulting in only restricted and narrow benefits. Therefore, there is a pressing need to find alternative chemotherapeutic drugs for combating cancers. Plants have been used since ages in medicine, and by the dawn of 19th century, various potent and promising anti-cancer products have been derived from plants. Strigolactones (SLs) are a novel class of phytohormones involved in regulating the branching of shoots. Recently, many novel synthesized SL analogues have been found to be effective against solid and non-solid tumours. These hormones have been reported to have a unique mechanism of inhibiting cancer cells by lowering their viability and promoting apoptosis and cell death at micromolar concentrations. Therefore, synthetic SL analogues could be future potent anti-cancer drug candidates. Further research is needed to identify and deduce the significance of these synthetic SL analogues.

In the present study, we investigated the hypolipidemic and hepatoprotective potential of the commercially available crushed Ajwa date seed-extract on the toxicity caused by the atorvastatin in high-fat diet (HFD)-induced hyperlipidemic rats. Male albino rats were divided into two main groups, Group I (normal control) and Group II (HFD); Group II was further divided into four subgroups: Group IIa (HFD control), Group IIb (Atorvastatin: A10)-6 rats were administered with 10 mg/kg atorvastatin daily for 30 days, Group IIc (Ajwa seed extract: AJ)-6 rats were given 1000 mg/kg Ajwa seed extract daily for 30 days, Group IId (AJ + A10)-6 rats were given Ajwa seed extract 1000 mg/kg and Atorvastatin 10 mg/kg daily for 30 days. The data obtained suggested that Ajwa seed extract lowered the serum cholesterol level in HFD rats and demonstrated the hepatoprotective effect in combination with atorvastatin by reducing the levels of ALT and AST. In conclusion, it protected the tissues from the detrimental effects of hyperglycemia and enhanced antioxidant activity. Furthermore, the dose-limiting toxicity of atorvastatin may be reduced if the Ajwa seed extract is incorporated in the current treatment regimens to treat hyperlipidemia in hypercholesteremic individuals.

Curcumin is chemically known as diferuloylmethane, which is an important nutraceutical obtained from the yellow spice Curcuma longa. It has been used traditionally as a folklore medicine in countries like India, China and Thailand for nearly 2000 years without any prior knowledge of the mechanism of action. Cell-based studies and clinical trials that have been reported so far have provided evidence that curcumin could be effectively used as antimicrobial, anticancer, antidiabetic, antiinflammatory, antimalarial and antioxidant. There are more than 9400 articles published on this “magical molecule” till date. Furthermore, nearly 100 clinical trials have been done using curcumin, which demonstrated safety, efficacy and prophylactic activity of curcumin. On the molecular level, curcumin has shown to modulate several crucial and significantly interlinked pathways in rendering an optimistic outcome against life-threatening diseases like cancer, diabetes, lupus nephritis, and other autoimmune and neurodegenerative diseases. In this communication, the chemical structure, biological properties and possible molecular targets of curcumin have been reviewed along with some recent developments in drug delivery systems of curcumin.

Hepatocellular carcinoma (HCC) remains one of the leading causes of death worldwide. The complex etiology is attributed to many factors like heredity, cirrhosis, hepatitis infections or the dysregulation of the different molecular pathways. Nevertheless, the current treatment regimens have either severe side effects or tumors gradually acquire resistance upon prolonged use. Thus, developing a new selective treatment for HCC is the need of the hour. Many anticancer agents derived from plants have been evaluated for their cytotoxicity towards many human cancer cell lines. Strigolactones (SLs)-a newly discovered class of phytohormones, play a crucial role in the development of plant-root and shoot. Recently, many synthetic analogues of SLs have demonstrated pro-apoptotic effects on different cancer cell lines like prostate, breast, colon and lung. In this study, we tested synthetic SLs analogues on HCC cell line-HepG2 and evaluated their capability to induce cell proliferation inhibition and apoptosis. Primary WST-1 assays, followed by annexin-V/7AAD staining, demonstrated the anti-proliferative effects. The SLs analogues TIT3 and TIT7 were found to significantly reduce HepG2 cell viability in a dose- and time-dependent manner and induce apoptosis. Interestingly, though TIT3 and TIT7 strongly affected cancer cell proliferation, both compounds showed moderate anti-proliferative effect on normal cells. Further, migration of cancer cells was suppressed upon treatment with TIT3 and TIT7 in a wound healing assay. In summary, these findings suggest that two SLs analogues TIT3 and TIT7 exert selective inhibitory effects on cancer cells most likely through targeting microtubules. SLs analogues could be used in future as potential anti-cancer candidates in chemotherapy.

The polyamines putrescine, spermidine, and spermine are polycationic, alkyl polyamines which play a significant role in eukaryotic cell proliferation. The polyamine metabolism and function are dysregulated in tumor cells making them an attractive therapeutic target by employing polyamine analogs. These analogs have a high degree of similarity with the structure of polyamines but not with their function. Multidrug resistance is a major factor in the failure of many chemotherapeutic drugs which necessitates further research and exploration of better novel alternatives. In the present study, Twenty-six novel acylspermidine derivatives were synthesized and evaluated for their anti-proliferative and pro-apoptotic activities on human breast cancer cells and T-lymphoblastic leukemia cells. The cell proliferation and apoptosis assays using WST-1 and annexin-V/7AAD staining respectively suggest that Compound 1 (C19H41N3O2), Compound 7(C25H51N3O2) and Compound 8 (C29H59N3O) significantly reduced cancer cell viability in a dose- and time-dependent manner. Interestingly, compounds 7, 8 and 9 had slight or no effect on cell proliferation of non-cancerous cells. These studies speculate that these novel acylspermidine derivatives could be promising candidates in designing an anti-proliferative drug, targeting both solid and blood cancer cells.

Naturally occurring polyamines like Putrescine, Spermidine, and Spermine are polycations which bind to the DNA, hence stabilizing it and promoting the essential cellular processes. Many synthetic polyamine analogues have been synthesized in the past few years, which have shown cytotoxic effects on different tumours. In the present study, we evaluated the antiproliferative effect of a novel, acylspermidine derivative, (N-(4-aminobutyl)-N-(3-aminopropyl)-8-hydroxy-dodecanamide) (AAHD) on HepG2 cells. Fluorescence staining was performed with nuclear stain (Hoechst 33342) and acridine orange/ethidium bromide double staining. Dose and the time-dependent antiproliferative effect were observed by WST-1 assays, and radical scavenging activity was measured by ROS. Morphological changes such as cell shrinkage & blebbing were analyzed by fluorescent microscopy. It was found that AAHD markedly suppressed the growth of HepG2 cells in a dose- and time-dependent manner. It was also noted that the modulation of ROS levels confirmed the radical scavenging activity. In the near future, AAHD can be a promising drug candidate in chalking out a neoplastic strategy to control the proliferation of tumour cells. This study indicated that AAHD induced anti-proliferative and pro-apoptotic activities on HCC. Since AAHD was active at micromolar concentrations without any adverse effects on the healthy cells (Fibroblasts), it is worthy of further clinical investigations.