Curcumin application as an anti‐cancer drug is faced with several impediments. This study has developed a platform that facilitates the sustained release of curcumin, improves loading efficiency, and anti‐cancer activity. Montmorillonite (MMT) nanoparticles were added to chitosan (CS)‐agarose (Aga) hydrogel and then loaded with curcumin (Cur) to prepare a curcumin‐loaded nanocomposite hydrogel. The loading capacity increased from 63% to 76% by adding MMT nanoparticles to a chitosan‐agarose hydrogel. Loading the fabricated nanocomposite in the nanoniosomal emulsion resulted in sustained release of curcumin under acidic conditions. Release kinetics analysis showed diffusion and erosion are the dominant release mechanisms, indicating non‐fickian (or anomalous) transport based on the Korsmeyer‐Peppas model. FTIR spectra confirmed that all nanocomposite components were present in the fabricated nanocomposite. Besides, XRD results corroborated the amorphous structure of the prepared nanocomposite. Zeta potential results corroborated the stability of the fabricated nanocarrier. Cytotoxicity of the prepared CS‐Aga‐MMT‐Cur on MCF‐7 cells was comparable with that of curcumin‐treated cells (p < 0.001). Moreover, the percentage of apoptotic cells increased due to the enhanced release profile resulting from the addition of MMT to the hydrogel and the incorporation of the fabricated nanocomposite into the nanoniosomal emulsion. To recapitulate, the current delivery platform improved loading, sustained release, and curcumin anti‐cancer effect. Hence, this platform could be a potential candidate to mitigate cancer therapy restrictions with curcumin.

A novel pH‐responsive nanoniosomal emulsion for sustained release of curcumin from a chitosan‐based nanocarrier: Emphasis on the concurrent improvement of loading, sustained release, and apoptosis induction

Helicobacter pylori infection is associated with chronic gastritis, peptic ulcers, and gastric cancer. The flavonoid compounds baicalin and baicalein found in many medicinal plants exhibit an anti-inflammatory effect. The administration of Lactobacillus strains reducing the risk of H. pylori infection is well accepted. In this study, the therapeutic effects against H. pylori infection of baicalin, baicalein, and L. rhamnosus JB3 (LR-JB3), isolated from a dairy product, were investigated. Compared to baicalin, baicalein exhibited stronger anti-H. pylori activity and cytotoxicity on human gastric cancer epithelial AGS cells. Baicalin and baicalein both suppressed the vacA gene expression of H. pylori and interfered with the adhesion and invasion ability of H. pylori to AGS cells, as well as decreased H. pylori-induced interleukin (IL)-8 expression. In the mice infection model, high dosages of baicalin and baicalein inhibited H. pylori growth in the mice stomachs. Serum IL-1β levels and H. pylori-specific serum IgM and IgA levels in mice treated with baicalin and baicalein were decreased. Moreover, a synergistic therapeutic effect of baicalein and LR-JB3 on eradicating H. pylori infections was observed. Thus, administrating baicalin, baicalein, or LR-JB3 for an H. pylori infection could offer similar therapeutic effects to administering antibiotics while not disturbing the balance of gut microbiota. This study revealed the effects of baicalin, baicalein, and LR-JB3 on attenuating the virulence of H. pylori. The synergistic effect with baicalein and LR-JB3 provides the experimental rationale for testing the reliability, safety, and efficacy of this approach in higher animals and perhaps ultimately in humans to eradicate H. pylori infections. PRACTICAL APPLICATION: Baicalin and baicalein exert health promotion and avoidance of H. pylori infections by interfering with H. pylori growth and virulence. Lactobacillus rhamnosus JB3 was used to reduce the gastric inflammation caused by H. pylori infection.

Baicalin, Baicalein, and Lactobacillus Rhamnosus JB3 Alleviated Helicobacter pylori Infections in Vitro and in Vivo

Flavonoids are considered as pleiotropic, safe, and readily obtainable molecules. A large number of recent studies have proposed that flavonoids have potential in the treatment of tumors by the modulation of autophagy. In many cases, flavonoids suppress cancer by stimulating excessive autophagy or impairing autophagy flux especially in apoptosis-resistant cancer cells. However, the anti-cancer activity of flavonoids may be attenuated due to the simultaneous induction of protective autophagy. Notably, flavonoids-triggered protective autophagy is becoming a trend for preventing cancer in the clinical setting or for protecting patients from conventional therapeutic side effects in normal tissues. In this review, focusing on the underlying autophagic mechanisms of flavonoids, we hope to provide a new perspective for clinical application of flavonoids in cancer therapy. In addition, we highlight new research ideas for the development of new dosage forms of flavonoids to improve their various pharmacological effects, establishing flavonoids as ideal candidates for cancer prevention and therapy in the clinic.

https://www.mdpi.com/2076-3921/10/7/1138/pdf

The Multifaceted Role of Flavonoids in Cancer Therapy: Leveraging Autophagy with a Double-Edged Sword.

Several studies have reported neuroprotective effects by natural products. A wide range of natural compounds have been investigated, and some of these may play a beneficial role in Alzheimer’s disease (AD) progression. Matrix metalloproteinases (MMPs), a family of zinc-dependent endopeptidases, have been implicated in AD. In particular, MMP-2 and MMP-9 are able to trigger several neuroinflammatory and neurodegenerative pathways. In this review, we summarize and discuss existing literature on natural marine and terrestrial compounds, as well as their ability to modulate MMP-2 and MMP-9, and we evaluate their potential as therapeutic compounds for neurodegenerative and neuroinflammatory diseases, with a focus on Alzheimer’s disease.

Natural Marine and Terrestrial Compounds as Modulators of Matrix Metalloproteinases-2 (MMP-2) and MMP-9 in Alzheimer's Disease.

As a multifactorial disease, treatment of cancer depends on understanding unique mechanisms involved in its progression. The cancer stem cells (CSCs) are responsible for tumor stemness and by enhancing colony formation, proliferation as well as metastasis, and these cells can also mediate resistance to therapy. Furthermore, the presence of CSCs leads to cancer recurrence and therefore their complete eradication can have immense therapeutic benefits. The present review focuses on targeting CSCs by natural products in cancer therapy. The growth and colony formation capacities of CSCs have been reported can be attenuated by the dietary agents. These compounds can induce apoptosis in CSCs and reduce tumor migration and invasion via EMT inhibition. A variety of molecular pathways including STAT3, Wnt/β-catenin, Sonic Hedgehog, Gli1 and NF-κB undergo down-regulation by dietary agents in suppressing CSC features. Upon exposure to natural agents, a significant decrease occurs in levels of CSC markers including CD44, CD133, ALDH1, Oct4 and Nanog to impair cancer stemness. Furthermore, CSC suppression by dietary agents can enhance sensitivity of tumors to chemotherapy and radiotherapy. In addition to in vitro studies, as well as experiments on the different preclinical models have shown capacity of natural products in suppressing cancer stemness. Furthermore, use of nanostructures for improving therapeutic impact of dietary agents is recommended to rapidly translate preclinical findings for clinical use.

Raj Savla

Papers

Path of Silibinin from diet to medicine: A dietary polyphenolic flavonoid having potential anti-cancer therapeutic significance.

Baicalein: A metabolite with promising antineoplastic activity

Emodin: A metabolite that exhibits anti-neoplastic activities by modulating multiple oncogenic targets.