Research Article Anticancer and antimicrobial activities of diosmin

Ciriminna R., Petri G.L., Angellotti G., Luque R., Fabiano-Tixier A., Meneguzzo F., Pagliaro M.

ABSTRACTCitrus flavonoids are highly bioactive compounds exerting numerous health benefits including anticancer, antioxidant, antimicrobial, anti‐inflammatory, mitoprotective, and neuroprotective activity. Research on their broad‐scope bioactivity experienced a renaissance in the early 2000s, and further accelerated after COVID‐19, including research on their antimicrobial properties. Summarizing selected research achievements on the antimicrobial activity of the main Citrus flavonoids, this study aims to provide a unified picture on the antimicrobial properties of these valued compounds that will hopefully assist in the development of flavonoid‐based antimicrobials, including antibacterial treatments suitable for clinical use minimizing antimicrobial resistance.

Rampogu S., Al-antari M.A., Oh T.H., Shaik B.

Breast cancer is one of the predominant causes of mortality in women worldwide. Although therapeutics such as surgery, chemotherapy, hormonal therapy, and radiotherapy have been used, they are associated with adverse effects or multidrug resistance. The use of natural compounds is a promising strategy, owing to their abundance and medicinal value. This review focuses on six natural compounds, namely cinnamaldehyde, diosmin, taxifolin, phloretin, arctigenin, and eugenol, and details their mechanisms of breast cancer inhibition based on in vitro and in vivo studies. These compounds generally promote apoptosis and cell cycle arrest, hinder metastasis and invasion, and decrease tumor growth. This review reinforces the use of natural compounds as therapeutics for breast cancer from their preclinical studies. These compounds might be promising for drug development due to their abundance, high reliability, and safety.

Rajasekar M., Suresh K., Theerthu A., Pugazhendhi R., Sivakumar K.

The present study aims to explore the anticancer efficacy of Diosmin by inducing mitochondrial-mediated apoptosis in human epidermoid carcinoma cells (Hep-2). This is done by cell line assays and studying crucial inflammatory and apoptotic signaling molecules. The cytotoxicity property of Diosmin was evaluated by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Marker expression study was done by western blotting for studying apoptotic markers like Bax, Bcl-2, p53, Bak, and Bcl-xl, proinflammatory cytokine (TNF-α), interleukins (IL-1, IL-6, IL-8), and signal transduction (STAT-3). The docking study confirms the affinity of Diosmin with apoptotic and important markers. Through the MTT assay, a dose-dependent cytotoxic effect of Diosmin was unveiled, with an IC50 value of effective inhibition of cell proliferation. Diosmin treatment resulted in noteworthy downregulation of Bcl-xl, Bak, Bcl-2, IL-1, 6, 8, TNF-α, and STAT-3 while upregulating the p53 and Bax expression levels, highlighting its inhibitory role in inducing apoptosis. Docking studies further exposed robust binding affinities between Diosmin and target apoptotic proteins, suggesting its efficacy in disrupting cellular functions and inflammatory signaling pathways in Hep-2 cells. The cytotoxic effects on Hep-2 cells and suggested activation of Bax, p53, and inhibition of Bcl-xl, Bak, Bcl-2, IL-1, 6, 8, TNF-α, as well as STAT-3 lead to the activation of mitochondrial-mediated apoptosis in Diosmin-treated Hep-2 cells. Further, its anti-inflammatory properties locate Diosmin as a conclusive compound for further studies for effective oral and other related squamous carcinoma treatments.

Arora S., Srivastava S., Verma U., Sheoran S., Kumar N.

Cancer continues to be a leading cause of mortality worldwide, with rising prevalence linked to genetic abnormalities, epigenetic alterations, detrimental lifestyle choices, and an aging demographic. Conventional cancer treatments, such as chemotherapy, radiation, and immunotherapy, while somewhat successful, sometimes entail significant adverse effects, drug resistance, and restricted access to tumor tissues, especially in advanced-stage tumors. These problems have exacerbated the quest for alternative and complementary therapy. Flavonoids, a category of naturally occurring polyphenolic chemicals present in several fruits, vegetables, and medicinal plants, have garnered significant interest for their anticancer properties. Compounds such as kaempferol, quercetin, apigenin, and diosmin demonstrate several modes of action, including antioxidant properties, reduction of tumor cell growth, activation of apoptosis, and suppression of angiogenesis and metastasis. Moreover, flavonoids have demonstrated the capacity to regulate critical signaling pathways implicated in cancer advancement, including the PI3K/Akt, mTOR, and JAK/STAT pathways. Recent breakthroughs in nanotechnology have improved the bioavailability and targeted distribution of flavonoids, hence enhancing their medicinal efficiency. This chapter underscores the potential of flavonoids in cancer prevention and treatment, examines the incorporation of flavonoid-based nanoparticles in augmenting cancer therapy, and stresses the necessity for additional research to assess their safety, pharmacokinetics, and synergistic interactions with standard therapies.

Rahman L., Talha Khalil A., Ahsan Shahid S., Shinwari Z.K., Almarhoon Z.M., Alalmaie A., Sharifi‐Rad J., Calina D.

AbstractDiosmin, a potent bioflavonoid derived from citrus fruits, has gained significant attention for its anticancer potential, reflecting a critical need in the ongoing battle against cancer. Amidst increasing cancer incidence, the quest for safer and more effective treatments has brought diosmin to the forefront, given its unique pharmacological profile distinct from other flavonoids. Diosmin's anticancer mechanisms are multifaceted, involving apoptosis induction, angiogenesis inhibition, and metastasis prevention. Extensive research encompassing cellular studies, animal models, and limited clinical trials underscores its efficacy not only against cancer but also in managing chronic venous insufficiency and hemorrhoids, attributing to its anti‐inflammatory properties. Furthermore, diosmin exhibits low toxicity and complements conventional chemotherapy, proposing its utility as an adjunct therapy in cancer treatment protocols. The review delves into the specific anticancer advantages of diosmin, distinguishing it from the broader flavonoid category. It provides a detailed analysis of its implications in preclinical and clinical settings, advocating for its consideration in the oncological therapeutic arsenal. By juxtaposing diosmin with other herbal medicines, the review offers a nuanced perspective on its role within the wider context of natural anticancer agents, emphasizing the need for further clinical research to substantiate its efficacy and safety in oncology.

Rajasekar M., Bhuvanesh P., Varada P., Selvam M.

A group of secondary plant metabolites known as flavonoids, which are polyphenolic chemicals, have a variety of pharmacological properties, including anti-cancer properties. By modifying various enzymes and receptors in signal transduction pathways related to cellular proliferation, differentiation, apoptosis, inflammation, angiogenesis, metastasis, and reversal of multi-drug resistance, they have been reported to interfere with the beginning, promoting, and progression of cancer. Flavonoids are being researched for their possible using cancer treatments due to their numerous molecular modes of action. By offering fresh perspectives on the variables, regulation, and molecular mechanisms as well as their major protein interactions, the current review highlights the therapeutic promise of nano-encapsulation flavonoids and their synthetic analogs as anti-cancer medicines.

Gwozdzinski L., Bernasinska-Slomczewska J., Wiktorowska-Owczarek A., Kowalczyk E., Pieniazek A.

Diosmin and bromelain are bioactive compounds of plant origin with proven beneficial effects on the human cardiovascular system. We found that diosmin and bromelain slightly reduced total carbonyls levels and had no effect on TBARS levels, as well as slightly increased the total non-enzymatic antioxidant capacity in the RBCs at concentrations of 30 and 60 µg/mL. Diosmin and bromelain induced a significant increase in total thiols and glutathione in the RBCs. Examining the rheological properties of RBCs, we found that both compounds slightly reduce the internal viscosity of the RBCs. Using the MSL (maleimide spin label), we revealed that higher concentrations of bromelain led to a significant decrease in the mobility of this spin label attached to cytosolic thiols in the RBCs, as well as attached to hemoglobin at a higher concentration of diosmin, and for both concentrations of bromelain. Both compounds tended to decrease the cell membrane fluidity in the subsurface area, but not in the deeper regions. An increase in the glutathione concentration and the total level of thiol compounds promotes the protection of the RBCs against oxidative stress, suggesting that both compounds have a stabilizing effect on the cell membrane and improve the rheological properties of the RBCs.

Şimşek E., Koçak O., Yıldırım K., Kuruoğlu A., Taşkın N.D., Bozkurt S., İmir N., Ataş C., Akçit E.T., Çoban M., Çoban A.Y.

This study examined the antiangiogenic capacity of diosmin in vitro and their interactions with certain important receptors related to cancer and infectious diseases via molecular docking. Diosmin, a naturally occurring flavone glycoside, largely found in citrus fruits, exhibits potentially antiangiogenic properties especially interacting with both VEGF and VEGFR. Treatment with certain doses of diosmin caused a reduction with a ratio of 22–68% on VEGF levels as compared to non-treated control groups. Western blotting and real-time PCR results demonstrated that protein expression of VEGF was downregulated in a dose- and time-dependent manner. On the other hand, we aimed to check the possible interaction of diosmin with VEGF, VEGFR, HER, PR, ER, and Omp-a, receptor proteins. According to our molecular docking results, diosmin effectively binds these receptors and probably this could be one of the possible reasons for its anti-angiogenic and anti-microbial properties.

Anwer S.T., Mobashir M., Fantoukh O.I., Khan B., Imtiyaz K., Naqvi I.H., Rizvi M.M.

The creation of novel anticancer treatments for a variety of human illnesses, including different malignancies and dangerous microbes, also potentially depends on nanoparticles including silver. Recently, it has been successful to biologically synthesize metal nanoparticles using plant extracts. The natural flavonoid 3,3′, 4′, 5,5′, and 7 hexahydroxyflavon (myricetin) has anticancer properties. There is not much known about the regulatory effects of myricetin on the possible cell fate-determination mechanisms (such as apoptosis/proliferation) in colorectal cancer. Because the majority of investigations related to the anticancer activity of myricetin have dominantly focused on the enhancement of tumor cell uncontrolled growth (i.e., apoptosis). Thus, we have decided to explore the potential myricetin interactors and the associated biological functions by using an in-silico approach. Then, we focused on the main goal of the work which involved the synthesis of silver nanoparticles and the labeling of myricetin with it. The synthesized silver nanoparticles were examined using UV-visible spectroscopy, dynamic light scattering spectroscopy, Fourier transform infrared spectroscopy, and scanning electron microscopy. In this study, we have investigated the effects of myricetin on colorectal cancer where numerous techniques were used to show myricetin’s effect on colon cancer cells. Transmission Electron Microscopy was employed to monitor morphological changes. Furthermore, we have combined the results of the colorectal cancer gene expression dataset with those of the myricetin interactors and pathways. Based on the results, we conclude that myricetin is able to efficiently kill human colorectal cancer cell lines. Since, it shares important biological roles and possible route components and this myricetin may be a promising herbal treatment for colorectal cancer as per an in-silico analysis of the TCGA dataset.

Huwait E., Mobashir M.

Because of their medicinal characteristics, effectiveness, and importance, plant-derived flavonoids have been a possible subject of research for many years, particularly in the last decade. Plants contain a huge number of flavonoids, and Diosmin, a flavone glycoside, is one of them. Numerous in-vitro and in-vivo studies have validated Diosmin’s extensive range of biological capabilities which present antioxidative, antihyperglycemic, anti-inflammatory, antimutagenic, and antiulcer properties. We have presented this review work because of the greater biological properties and influences of Diosmin. We have provided a brief overview of Diosmin, its pharmacology, major biological properties, such as anti-cancer, anti-diabetic, antibacterial, anticardiovascular, liver protection, and neuroprotection, therapeutic approach, potential Diosmin targets, and pathways that are known to be associated with it.

Devika M.S., Vysakh A., Vijeesh V., Jisha N., Ruby P.M.