Involvement of Resveratrol against Brain Cancer: A Combination Strategy with a Pharmaceutical Approach.

A brain tumor (BT) is a condition in which there is growth or uncontrolled development of the brain cells, which usually goes unrecognized or is diagnosed at the later stages. Since the mechanism behind BT is not clear, and the various physiological conditions are difficult to diagnose, the success rate of BT is not very high. This is the central issue faced during drug development and clinical trials with almost all types of neurodegenerative disorders. In the first part of this review, we focus on the concept of brain tumors, their barriers, and the types of delivery possible to target the brain cells. Although various treatment methods are available, they all have side effects or toxic effects. Hence, in the second part, a correlation was made between the use of resveratrol, a potent antioxidant, and its advantages for brain diseases. The relationship between brain disease and the blood-brain barrier, multi-drug resistance, and the use of nanomedicine for treating brain disorders is also mentioned. In short, a hypothetical concept is given with a background investigation into the use of combination therapy with resveratrol as an active ingredient, the possible drug delivery, and its formulation-based approach.

5-Fluorouracil and Curcumin Combination Coated with Pectin and Its Strategy towards Titanium Dioxide, Dimethylhydrazine Colorectal Cancer Model with the Evaluation of the Blood Parameters.

Colorectal cancer is considered the third most common cancer and the second leading cause of death globally. It has been proven that titanium dioxide nanoparticles produce oxidative stress and can lead to chronic inflammation, which could turn into diseases like cancer, cardiovascular disorders, diabetes, and so on. To evaluate the effect of 5-fluorouracil (5-FU) curcumin (CUR) conjugate coated with pectin on colorectal cancer induced by titanium dioxide nanoparticles (TiO2-NPs) and dimethylhydrazine (DMH), male rats were administered TiO2-NPs (5 mg/kg) orally and DMH (1 mg/kg) peritoneally for 70 days and treated with 5-FU (60 mg/kg) and CUR (240 mg/kg) conjugate (1:4 ratio) coated with pectin. The bodyweight of the animals was evaluated, and the blood sugar level was calculated. Further blood and plasma analyses were conducted. Hematological parameters, antioxidant parameters, and biochemical estimation were taken into consideration. The TiO2-NPs level in the blood and colorectal region was also calculated. With the induction of colon cancer using TiO2-NPs and DMH, a significant increase in the body weight of the animals was seen; eventually, with treatment, it was reduced. The bodyweight increase was due to an increase in the blood sugar level. There were also significant changes in the hematological parameters and biochemical estimation reports when comparing those of the positive control, negative control, and treated groups. No significant effect on biochemical estimation reports was seen. Conclusions: These reports suggest that 5-FU CUR conjugate coated with pectin helps in the management of colorectal cancer induced by TiO2-NPs and DMH.

Multidrug Resistance in Cancer Cells: Focus on a Possible Strategy Plan to Address Colon Carcinoma Cells.

Even though various treatment methods are available for cancer, the death curve is not reducing. The diagnosis of cancer at the fourth stage and drug resistance are the leading reasons for treatment failure and lower survival rates. In this review article, we summarize the possible pitfalls during cancer treatment in general, which mainly include multidrug resistance, and propose a hypothesis for colorectal cancer specifically. We also evaluate multidrug resistance in cancer in general and colorectal cancer in particular and hypothesize a concept based on combination therapy with 5-fluorouracil, curcumin, and lipids for the possible management of colorectal cancer. In addition, a hypothetical approach, combining a synthetic agent and a natural chemotherapeutic agent, to treating colorectal cancer is also discussed. This hypothesis could improve the management of colorectal cancer.

Multidrug Resistance of Cancer Cells and the Vital Role of P-Glycoprotein.

P-glycoprotein (P-gp) is a major factor in the multidrug resistance phenotype in cancer cells. P-gp is a protein that regulates the ATP-dependent efflux of a wide range of anticancer medicines and confers resistance. Due to its wide specificity, several attempts have been made to block the action of P-gp to restore the efficacy of anticancer drugs. The major goal has been to create molecules that either compete with anticancer medicines for transport or function as a direct P-gp inhibitor. Despite significant in vitro success, there are presently no drugs available in the clinic that can "block" P-gp-mediated resistance. Toxicity, unfavourable pharmacological interactions, and a variety of pharmacokinetic difficulties might all be the reason for the failure. On the other hand, P-gp has a significant effect in the body. It protects the vital organs from the entry of foreign bodies and other toxic chemicals. Hence, the inhibitors of P-gp should not hinder its action in the normal cells. To develop an effective inhibitor of P-gp, thorough background knowledge is needed in this field. The main aim of this review article was to set forth the merits and demerits of the action of P-gp on cancer cells as well as on normal cells. The influence of P-gp on cancer drug delivery and the contribution of P-gp to activating drug resistance were also mentioned.

5-fluorouracil and curcumin with pectin coating as a treatment regimen for titanium dioxide with dimethylhydrazine-induced colon cancer model.

Colorectal cancer was inducted in Wister rats using titanium dioxide nanoparticles (TiO2NPs) and dimethylhydrazine (DMH) and treatment using 5-fluorouracil (5-FU) and curcumin (CUR), individually and following a synergistic approach. Compatibility studies are evaluated by using FT-IR spectra analysis, and Vero cell lines as well as HCT-116 cell lines are used for evaluating the synergistic approach. It was then followed by induction of colorectal cancer in rats for 70 days and treatment using 5-FU and CUR with pectin coating (individually and in combination) for 28 days. The reports state that 5-FU and CUR combination was found to be compatible. The synergistic effect was evaluated for1:1, 1:2, 1:4, and 2:1 ratio of 5-FU:CUR, where 1:4 ratio shows a CI50 value of 0.853, selected further for the animal studies. The 1:4 ratio of 5-FU and CUR (50:200) shows to be effective for the treatment of colorectal cancer within 28 days, proven using histopathology report, bodyweight analysis, and hematological reports. 5-FU and CUR (1:4) ratio with pectin coating was proven effective for the treatment of colorectal cancer induced by TiO2NPs with DMH and was found to produce a synergistic effect.

Potential innovation against Alzheimer's disorder: a tricomponent combination of natural antioxidants (vitamin E, quercetin, and basil oil) and the development of its intranasal delivery.

Alzheimer's disorder (AD) is very difficult to manage and treat. The complexity of the brain, the blood-brain barrier influencing a multitude of parameters/biomarkers, as well as numerous other factors involved often contribute to the decline in the chances of treatment success. Development of the new drug moiety also takes time, being necessary to consider both its toxicity and related issues. As a strategic plan, a combined strategy is being developed and considered to address AD pathology using several approaches. A combination of vitamin E, quercetin, and basil oil in a nano-based formulation is designed to be administered nasally. The antioxidant present in these natural-based products helps to treat and alleviate AD if a synergistic approach is considered. The three active substances mentioned above are well known for the treatment of neurodegenerative disorders. The nanoformulation helps the co-delivery of the drug moiety to the brain through the intranasal route. In this review, a correlation and use of vitamin E, quercetin, and basil oil in a nano-based formulation is described as an effective way to treat AD. The intranasal administration of drugs is a promising approach for the treatment of neurodegenerative and mental disorders, as this route is non-invasive, enhances the bioavailability, allows a drug dose reduction, bypasses the blood-brain barrier, and reduces the systemic undesired effect. The use of natural products is generally considered to be just as safe; therefore, by using this combined approach, the level of toxicity can be minimized.

Chemo-Preventive Action of Resveratrol: Suppression of p53-A Molecular Targeting Approach.

Extensive experimental, clinical, and epidemiological evidence has explained and proven that products of natural origin are significantly important in preventing and/or ameliorating various disorders, including different types of cancer that researchers are extremely focused on. Among these studies on natural active substances, one can distinguish the emphasis on resveratrol and its properties, especially the potential anticancer role. Resveratrol is a natural product proven for its therapeutic activity, with remarkable anti-inflammatory properties. Various other benefits/actions have also been reported, such as cardioprotective, anti-ageing, antioxidant, etc. and its rapid digestion/absorption as well. This review aims to collect and present the latest published studies on resveratrol and its impact on cancer prevention, molecular signals (especially p53 protein participation), and its therapeutic prospects. The most recent information regarding the healing action of resveratrol is presented and concentrated to create an updated database focused on this topic presented above.

Curcumin Nanoparticles as Promising Therapeutic Agents for Drug Targets.

Curcuma longa is very well-known medicinal plant not only in the Asian hemisphere but also known across the globe for its therapeutic and medicinal benefits. The active moiety of Curcuma longa is curcumin and has gained importance in various treatments of various disorders such as antibacterial, antiprotozoal, cancer, obesity, diabetics and wound healing applications. Several techniques had been exploited as reported by researchers for increasing the therapeutic potential and its pharmacological activity. Here, the dictum is the new room for the development of physicochemical, as well as biological, studies for the efficacy in target specificity. Here, we discussed nanoformulation techniques, which lend support to upgrade the characters to the curcumin such as enhancing bioavailability, increasing solubility, modifying metabolisms, and target specificity, prolonged circulation, enhanced permeation. Our manuscript tried to seek the attention of the researcher by framing some solutions of some existing troubleshoots of this bioactive component for enhanced applications and making the formulations feasible at an industrial production scale. This manuscript focuses on recent inventions as well, which can further be implemented at the community level.

Role of Phytonutrients in Nutrigenetics and Nutrigenomics Perspective in Curing Breast Cancer.

Breast cancer (BC) is one of the most common type of cancer and an important contributor to female mortality. Several genes and epigenetic modifications are involved in the development and progression of BC. Research in phytochemistry, nutrigenomics, and nutrigenetics has provided strong evidence that certain phytonutrients are able to modulate gene expression at transcriptional and post-transcriptional levels. Such phytonutrients may also be beneficial to prevent and treat BC. In this review, we will focus on the nutrigenomic effects of various phytochemicals including polyphenols, phytosterols, terpenoids, alkaloids, and other compounds from different sources. Overall, these phytonutrients are found to inhibit BC cell proliferation, differentiation, invasion, metastasis, angiogenesis, and induce apoptotic cell death by targeting various molecular pathways. They also alter epigenetic mechanisms and enhance the chemosensitivity and radiosensitivity of cancer cells. Such phytochemicals may be used for the effective management of BC patients in the clinical setting in the future. The present article aims to summarize the specific molecular pathways involved in the genetic effects of phytochemicals in BC.

Multiple strategies with the synergistic approach for addressing colorectal cancer.

Cancer treatment is improving widely over time, but finding a proper defender to beat them seems like a distant dream. The quest for identification and discovery of drugs with an effective action is still a vital work. The role of a membrane protein called P-glycoprotein, which functions as garbage chute that efflux the waste, xenobiotics, and toxins out of the cancer cells acts as a major reason behind the therapeutic failure of most chemotherapeutic drugs. In this review, we mainly focused on a multiple strategies by employing 5-Fluorouracil, curcumin, and lipids in Nano formulation for the possible treatment of colorectal cancer and its metastasis. Eventually, multidrug resistance and angiogenesis can be altered and it would be helpful in colorectal cancer targeting.We have depicted the possible way for the depletion of colorectal cancer cells without disturbing the normal cells. The concept of focusing on multiple pathways for marking the colorectal cancer cells could help in activating one among the pathways if the other one fails. The activity of the 5-Fluorouracil can be enhanced with the help of curcumin which acts as a chemosensitizer, chemotherapeutic agent, and even for altering the resistance. As we eat to survive, so do the cancer cells. The cancer cells utilize the energy source to stay alive and survive. Fatty acids can be used as the energy source and this concept can be employed for targeting the colorectal cancer cells and also for altering the resistant part.

Curcumin as a great contributor for the treatment and mitigation of colorectal cancer.

Cancer is one of the life-taking diseases worldwide and among cancer-related death; colorectal cancer is the third most. Though conventional methods of treatment are available, multidrug resistance and side effects are predominant. Physicians and scientists are working side by side to develop an effective medicament, which is safe and cost-effective. However, most failures are obtained when focused on the clinical perspective. This review mainly brings out the correlation between the curcumin and its use for the mitigation of colorectal cancer, the use of curcumin as a chemotherapeutic agent, chemosensitizer, and in a combination and synergistic approach. The pharmacokinetics and pharmacodynamics properties of curcumin and its formulation approach helps in giving an idea to develop new approaches for the treatment of colorectal cancer using curcumin.

Incorporation of natural assumption to deal with cancer.

The current state of the art for the use of natural ingredients for cancer therapy is by reviewing the publications and findings associated with cancer research with the employment of flavonoids. Cancer is the most furious disease making fear in the eyes of mankind. Though various treatment methods are prevalent, the patient's choices are shifting from synthetic treatment strategy to the natural ones. The plant-based metabolites are used very often in our life as a food additive and also as a medicine for primary health care. The safety profile and its efficacy add on advantage for the incorporation of the natural products separately or in combination as a remedy for cancer. Flavonoids, the plant-based metabolites are proven for their anti-inflammatory, anti-oxidant, and anti-cancer properties. Their chemotherapeutic and chemosensitizing power had made it interesting for the researchers to dig more on the health benefits of the flavonoids and incorporating it in a holistic approach, with its natural benefits to relieve the pain and the symptoms of the patient suffering from various medical conditions. The predominant approach for the management of cancer is by following safe and effective treatment modality. In this review, we mentioned the benefits of the flavonoids for the management of various cancers and its potency as a chemotherapeutic agent and as the chemosensitizer. Our mother nature had given remedies to cure various diseases in both human beings and animals by it; we just need to find out the sources and access to them.

Will the polyphenol and adapalene combination be a good strategy on acne vulgaris?

Acne vulgaris is a common disease which affects about 85% of the population. Various topical drugs are available, but the retinoid derivatives are mostly taken into consideration. They are used as a first-line treatment drugs. However, they also have few side effects. Whereas, adapalene which is a third generation topical retinoid has fewer side effects compared to other derivatives. In this, we hypothesize that the combination therapy of adapalene and flavonoid could improve the efficacy and thereby it can also decrease the treatment time. Since, flavonoids possess multiple activities we assume that it can improve the action of the drug by showing a synergistic activity. Moreover, when we incorporate these two drugs in nanoemulgel, it can easily penetrate into the skin and produce its therapeutic action. Hence, we assume that if this hypothesis proves to be correct then this method will be an effective one in treating acne (pustule).

Can curcumin along with chemotherapeutic drug and lipid provide an effective treatment of metastatic colon cancer and alter multidrug resistance?

Cancer is one of the most deadly diseases spreading all over the world and a major cause of fear in the society. Colon cancer is the 4th most common cancer causing death in both male and female equally, mainly caused due to the improper diet plans, consumption of the red meat and lack of exercise. Although the design of the chemotherapeutic drugs is well advanced, many of them developed resistance towards the cancer cells. The major reason behind the drug resistance in the colon cancer cells is due to the action exhibited by P-gp, which belongs to a member of ABC transporter family. P-glycoprotein (P-gp) effluxes the drug from its entry into the cancer cells, by treating it as a foreign body and hence decreases the therapeutic concentration of chemotherapeutic drugs inside the cancer cells. For overcoming this scenario, we posit the use of the curcumin (as a flavonoid) along with the lipid and the chemotherapeutic drug to provide an effective therapy and to overcome the possible issues associated with the failure in the therapy. Curcumin possesses dual mode of actions as a chemosensitizing agent and also as a chemotherapeutic drug. It generally acts as a chemosensitizer which can alter or inhibit the efflux pump exhibited by P-gp and provide a pathway for the entry of the chemotherapeutic drug into the cancer cells. Lipids have the potential to overcome the Multidrug resistance (MDR) and related issues; in addition, lipids are used for targeting colon cancer cells and also can act during the metastatic condition of the cancer which is hypothesised to be proven by using various studies. If our hypothesis is proven, the use of curcumin with lipids and the chemotherapeutic drug in a novel combination will reduces the majority of the issues related to the multidrug resistance, the recurrence and the spread of cancer could be overcome in a safe and effective manner.

Flavonoids as adjuvant in psoralen based photochemotherapy in the management of vitiligo/leucoderma.

Vitiligo is a disorder characterized by the decrease in melanin pigment of skin. This depigmenting disorder has prevalence among worldwide, irrespective of age and sex. There is an existence of different treatment modalities for the management of vitiligo. But irrespective of treatment methods, the main drawback in the management of vitiligo is the occurrence of side effects during the implication of treatment. Among the treatment modalities, photochemotherapy seems to be the better choice of treatment for vitiligo. Photochemotherapy involves the usage of UV rays for photoactivation of the drug to cause photosensitization of skin which in turn leads to repigmentation. The main aim of the study is to develop novel combination strategy of lipid based nanoemulsion gel for the treatment of leucoderma using trimethylpsoralen and flavonoid. We assume that if this hypothesis of combination therapy proves successful it can be used as an additional novel treatment strategy in the management of vitiligo.