The effect of environmental stressors on the anticancer potential of Amaranthus hypochondriacus aqueous extracts and fractions.

Some Amaranthus species have been shown to have pharmacological properties such as activity against cancer, and it is also used as a traditional herbal medicine in many rural parts of the world. The (3-(4,5-dimethylthiazol-2-Yl)-2,5-diphenyltetrazolium bromide assay was used as a screening tool to determine the approximate cell viability inhibitory concentrations of methanol and aqueous crude extracts of Amaranthus spp. The extracts were screened using small-cell lung cancer (H69V), hepatocellular carcinoma (HepG2/C3A) and non-cancerous kidney cells (Vero) cell lines. Viability was assessed following exposure to a series of concentrations of each extract and A. hypochondriacus showed cytotoxicity of 70.55 µg/mL against H69V with a Si index of 1.8. The fractionated aqueous extract of 40 °C-treated A. hypochondriacus under well-watered conditions had a higher viability inhibition on H69V and Vero cell lines compared to the A. caudatus, A. cruentus and A. spinosus crude extracts. In conclusion, A. hypochondriacus could serve as a potential source of anticancer phytoconstituents for drug development.

Influence of Drought and Heat Stress on Mineral Content, Antioxidant Activity and Bioactive Compound Accumulation in Four African Amaranthus Species.

Drought and heat stress is known to influence the accumulation of mineral content, antioxidant activity, phenolics, flavonoids and other bioactive compounds in many tolerant leafy vegetables. Amaranthus plants can tolerate adverse weather conditions, especially drought and heat. Therefore, evaluating the influence of drought and heat stress on commercially and medically important crop species like Amaranthus is important to grow the crop for optimal nutritional and medicinal properties. This study investigated the influence of drought and heat stress and a combination of both on the accumulation of phenolic and flavonoid compounds and the antioxidant capacity of African Amaranthus caudatus, A. hypochondriacus, A. cruentus and A. spinosus. Phenolic and flavonoid compounds were extracted with methanol and aqueous solvents and were quantified using liquid chromatography with tandem mass spectrometry (LC-MS/MS). Caffeic acid was the main phenolic compound identified in aqueous extracts of A. caudatus and A. hypochondriacus. Rutin was the most abundant flavonoid compound in all the Amaranthus species tested, with the highest concentration found in A. caudatus. The results suggest a strong positive, but species and compound-specific effect of drought and heat stress on bioactive compounds accumulation. We concluded that heat stress at 40 °C under well-watered conditions and combined drought and heat stress (at 30 °C and 35 °C) appeared to induce the accumulation of caffeic acid and rutin. Hence, cultivation of these species in semi-arid and arid areas is feasible.

Evaluation of the Antioxidant, Antidiabetic, and Anticholinesterase Potential of Biogenic Silver Nanoparticles from Khaya grandifoliola.

INTRODUCTION: In recent years, plant-mediated synthesis of silver nanoparticles has evolved as a promising alternative to traditional synthesis methods. In addition to producing silver nanoparticles with diverse biomedical potential, the biosynthesis approach is known to be inexpensive, rapid, and environmentally friendly. OBJECTIVE: This study was aimed at synthesizing silver nanoparticles using ethanolic stem and root bark extracts of Khaya grandifoliola and highlighting the biomedical potential of the nanoparticles by evaluating their antioxidant, antidiabetic and anticholinesterase effects in vitro. METHODS: Silver nanoparticles were prepared using ethanolic stem and root bark extracts of K. grandifoliola as precursors. The biogenic silver nanoparticles were characterized using UV-visible spectroscopy, fourier transform infrared spectroscopy, scanning electron microscopy and energydispersive X-ray analysis. Furthermore, 2,2-Diphenyl-1-picrylhydrazyl radical scavenging, ferric ion reducing antioxidant power, and nitric oxide scavenging assays were used to determine the antioxidant property of the nanoparticles. The antidiabetic potential of the nanoparticles was determined by evaluating their inhibitory effect on the activity of α-amylase and α-glucosidase. The anticholinesterase potential of the nanoparticles was determined by assessing their inhibitory effect on the activity of acetylcholinesterase and butyrylcholinesterase. RESULTS: UV-visible spectroscopy showed surface plasmon resonance bands between 425 and 450 nm. Scanning electron microscopy revealed almost round nanoparticles with a maximum size of 91 nm. Fourier transform infrared spectroscopy affirmed the role of the phytoconstituents present in K. grandifoliola as reducing and stabilizing agents. The biogenic silver nanoparticles showed remarkable antioxidant, antidiabetic, and anticholinesterase effects. CONCLUSION: Biogenic silver nanoparticles could be useful in biomedical and pharmacological applications.

Modified Gold Nanoparticles for Efficient Delivery of Betulinic Acid to Cancer Cell Mitochondria.

Advances in nanomedicine have seen the adaptation of nanoparticles (NPs) for subcellular delivery for enhanced therapeutic impact and reduced side effects. The pivotal role of the mitochondria in apoptosis and their potential as a target in cancers enables selective induction of cancer cell death. In this study, we examined the mitochondrial targeted delivery of betulinic acid (BA) by the mitochondriotropic TPP+-functionalized epigallocatechin gallate (EGCG)-capped gold NPs (AuNPs), comparing the impact of polyethylene glycol (PEG) and poly-L-lysine-graft-polyethylene glycol (PLL-g-PEG) copolymer on delivery efficacy. This included the assessment of their cellular uptake, mitochondrial localization and efficacy as therapeutic delivery platforms for BA in the human Caco-2, HeLa and MCF-7 cancer cell lines. These mitochondrial-targeted nanocomplexes demonstrated significant inhibition of cancer cell growth, with targeted nanocomplexes recording IC50 values in the range of 3.12-13.2 µM compared to that of the free BA (9.74-36.31 µM) in vitro, demonstrating the merit of mitochondrial targeting. Their mechanisms of action implicated high amplitude mitochondrial depolarization, caspases 3/7 activation, with an associated arrest at the G0/G1 phase of the cell cycle. This nano-delivery system is a potentially viable platform for mitochondrial-targeted delivery of BA and highlights mitochondrial targeting as an option in cancer therapy.

Co-Polymer Functionalised Gold Nanoparticles Show Efficient Mitochondrial Targeted Drug Delivery in Cervical Carcinoma Cells.

The mitochondria have recently become a novel target in the treatment of cancer. Targeted delivery by nanoparticles (NPs) has shown potential in enhancing existing therapeutic principles. With toxicity remaining a recurring issue, the green synthesis of inorganic NPs and modification with polymers may help to improve stability and biocompatibility. We synthesized epigallocatechin gallate (EGCG)-capped gold NPs (AuNPs), and functionalized with poly-D-lysine grafted polyethylene glycol (PDL-g-PEG), and the mitochondrial targeting triphenylphosphonium cation, and thereafter assessed their mitochondrial delivery capacity of paclitaxel in cancer cells in vitro. This PDL-g-PEG coated EGCG-AuNPs were further assessed for their laminin receptor avidity and mitochondrial localisation potential, upon functionalisation with the delocalised cation, triphenylphosphine. The laminin receptor dependent uptake and mitochondrial localisation of targeted T-Au(PDL-g-PEG) NPs were confirmed by ICP-OES and fluorescent microscopy. Their delivery of paclitaxel to the mitochondria of cancer cells elicited significant cytotoxicity especially in the human cervical carcinoma (HeLa) cell line, compared to the untargeted T-Au(PDL-g-PEG) and free drugs. Mechanistic studies implicated caspase dependent apoptosis as the mechanism of cell death. Our findings demonstrate the capacity of T-Au-[PDL-PEG] NPs to preferentially localize in the tumour mitochondria, and confirms the potential impact of subcellular targeting, especially to the mitochondria in cancer cells for an improvement in the therapeutic indices of these drugs.

Nanomedicines for Subcellular Targeting: The Mitochondrial Perspective.

BACKGROUND: Over the past decade, there has been a surge in the number of mitochondrialactive therapeutics for conditions ranging from cancer to aging. Subcellular targeting interventions can modulate adverse intracellular processes unique to the compartments within the cell. However, there is a dearth of reviews focusing on mitochondrial nano-delivery, and this review seeks to fill this gap with regards to nanotherapeutics of the mitochondria. METHODS: Besides its potential for a higher therapeutic index than targeting at the tissue and cell levels, subcellular targeting takes into account the limitations of systemic drug administration and significantly improves pharmacokinetics. Hence, an extensive literature review was undertaken and salient information was compiled in this review. RESULTS: From literature, it was evident that nanoparticles with their tunable physicochemical properties have shown potential for efficient therapeutic delivery, with several nanomedicines already approved by the FDA and others in clinical trials. However, strategies for the development of nanomedicines for subcellular targeting are still emerging, with an increased understanding of dysfunctional molecular processes advancing the development of treatment modules. For optimal delivery, the design of an ideal carrier for subcellular delivery must consider the features of the diseased microenvironment. The functional and structural features of the mitochondria in the diseased state are highlighted and potential nano-delivery interventions for treatment and diagnosis are discussed. CONCLUSION: This review provides an insight into recent advances in subcellular targeting, with a focus on en route barriers to subcellular targeting. The impact of mitochondrial dysfunction in the aetiology of certain diseases is highlighted, and potential therapeutic sites are identified.