Since the start of history, natural medicine has been of great interest and attention to humankind. A heap of empirical research indicates that spices have undoubtedly made our lives more interesting and may also make them longer. Capsicum is a highly regarded indispensable spice all over the globe for its umpteen culinary and medicinal facets. It has been used for more than 7000 years in Mexico and is believed to have originated in tropical Central America. Mainly, this botanical contains a good source of vitamin C, vitamin A, vitamin E, vitamin B5, potassium, magnesium, iron, calcium, phosphorus, and carotenoids. Interestingly, capsicum phenolic compounds are helpful in preventing and treating many ailments. So, it intends as a beneficial milestone in the pharmaceutical industry and a boon to humanity. This chapter highlights the tremendous pharmacological uses and health benefits of capsicum species and its active compounds in multifarious aspects.

Background: Capsaicin is a powerful phytochemical spotted in chilies, starkly tied up with a bunch of health benefits but its clinical applications in cancer therapy are limited due to its poor solubility, and low bioavailability. Nanotechnology offers a strategy to discover new formulations for hydrophobic agent. Aim: The main intent of the current research was to investigate the effect of Capsaicin encapsulated chitosan nanoparticles (CAP@CS-NP) on 7,12-Dimethylbenz(a)anthracene (DMBA) induced mammary carcinogenesis in rats. Methodology: Mammary tumor was induced in female rats by injecting DMBA (25mg/kg b.wt) at the first week of the experiment. After 7 weeks, CAP@CS-NP (4mg/kg b.wt) was administered orally to DMBA induced tumor bearing rats for 21 days (thrice per week). The experiment was terminated at the end of the 14th week and their plasma and tissue sections were analyzed. Results: We found that significantly elevated levels of lipid peroxidation and diminished levels of antioxidant status in plasma, liver and mammary tissues. Increased levels of detoxification phase I enzymes and dropped levels of phase II enzymes in liver and mammary tissues in DMBA induced tumor bearing rats. As a result, oral administration of CAP@CS-NP suppressed the tumor growth, significantly raised body weight and restored abnormal enzymatic levels to near normal ranges. Additionally, histopathological and immunohistochemical analysis were also confirmed that CAP@CS-NP protects DMBA mediated cellular disruption and also inhibits abnormal cell proliferation. Conclusion: These findings suggest that nano encapsulation of CAP@CS-NP could be useful in targeted drug delivery and act as a promising chemotherapeutic agent to treat mammary carcinogenesis.

Background: Diosgenin, a steroidal saponin spotted as a primary ingredient in many traditional Chinese medicines, has sparked the attention of researchers owing to its multi-targeted cytotoxicity towards a multitude of cancers. Regrettably, its true potential was bounded by its impoverished physicochemical properties. In order to fully exploit its ability, we plan to fabricate diosgenin into nanoparticle by encapsulating with biodegradable polymer chitosan. Aim: The current research intends to uncover the therapeutic potency of diosgenin encapsulated chitosan nanoparticles (DG@CS-NP) on 7,12dimethylbenz(a)anthracene (DMBA) induced rat mammary carcinoma by optimizing biochemical and histopathological modifications via attenuating Aryl hydrocarbon receptor (AhR) - nuclear factor erythroid-derived 2-related factors (Nrf-2) signaling. Methodology: Breast cancer was induced with a single dose of DMBA (25 mg/kg b.wt). Orally supplied DG 10mg/kg b.wt. and DG@CS-NP 5 mg/kg b.wt to DMBA-induced tumor-bearing rats shortly after tumor onset. After the experimental period, biochemical and histopathological studies were performed using mammary tissue sections. Furthermore, architectural immunohistochemistry was used to reveal the expression of AhR and Nrf-2 in experimental rats. Additionally, diosgenin interactions with these proteins were also evidently confirmed by molecular docking analysis. Result: We noticed that there is an elevated level of lipid peroxidative marker, phase-I detoxification enzymes, total cholesterol (TC), phospholipids (PL), triglycerides (TG), and free fatty acids (FFA) with boosted AhR expressions as well as diminished levels of enzymatic and non-enzymatic antioxidants and Phase – II detoxification enzymes with downtrodden Nrf-2 expressions in the mammary tissues of DMBA-induced rats. On the other contrary, oral dosing of DG@CS-NP 5 mg/kg b.wt, dramatically reverted them to near-normal tiers. Interestingly, molecular docking analyses also corroborate these insights by highlighting diosgenin's significant interactions with AhR and Nrf-2 targets. Conclusion: As an outcome of our observations, we conclude that nano-encapsulation of diosgenin is a potent targeted therapeutic candidate posing a massive impact on breast cancer than plain diosgenin.

Objective: The central motive of this study is to explore the therapeutic impact of Diosgenin encapsulated Chitosan nanoparticles (DG@CS-NP) on mammary carcinogenesis in female Sprague Dawley rats via modulating hormonal status, cell proliferation, inflammatory responses, and Apoptosis. Methods: 7,12-dimethylbenz(a)anthracene (DMBA) was administered subcutaneously near the mammary gland (25 mg/kg b. wt) to provoke mammary tumor in female Sprague Dawley rats. Following the progress of a tumor, DMBA-induced tumor-bearing rats were medicated orally with 5 mg/kg b. wt of DG@CS-NP. Consequently, the expression of ER, PR, PCNA, Cyclin D1, NF-κB, TNF-α, Bcl-2, Caspases-3, and p53 in experimental rats were revealed via architectural immunohistochemistry. Further, Diosgenin interactions with these proteins were evidently confirmed by molecular docking analysis. Results: As a result, we noticed diminished levels of ER, PR, PCNA, Cyclin D1, NF-κB, TNF-α, and Bcl-2 expressions in DG@CS-NP medicated rats as well as with elevated levels of Caspases-3 and p53 expressions. In DMBA rats, the expressions were vice versa. Additionally, molecular docking analyses support these outcomes by highlighting the strong interaction between Diosgenin and breast cancer targets. Conclusion: These reports prove that DG@CS-NP imposes its therapeutic impact by hormonal adjustments, downregulating proteins involved in inflammation and cellular proliferation, and thereby promotes apoptosis by impeding apoptotic inhibitors.

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