Medicinal plants have been used from ancient times for human healthcare as in the form of traditional medicines, spices, and other food components. Garlic (Allium sativum L.) is an aromatic herbaceous plant that is consumed worldwide as food and traditional remedy for various diseases. It has been reported to possess several biological properties including anticarcinogenic, antioxidant, antidiabetic, renoprotective, anti-atherosclerotic, antibacterial, antifungal, and antihypertensive activities in traditional medicines. A. sativum is rich in several sulfur-containing phytoconstituents such as alliin, allicin, ajoenes, vinyldithiins, and flavonoids such as quercetin. Extracts and isolated compounds of A. sativum have been evaluated for various biological activities including antibacterial, antiviral, antifungal, antiprotozoal, antioxidant, anti-inflammatory, and anticancer activities among others. This review examines the phytochemical composition, pharmacokinetics, and pharmacological activities of A. sativum extracts as well as its main active constituent, allicin.

Flavonoids are a class of natural substances present in plants, fruits, vegetables, wine, bulbs, bark, stems, roots, and tea. Several attempts are being made to isolate such natural products, which are popular for their health benefits. Flavonoids are now seen as an essential component in a number of cosmetic, pharmaceutical, and medicinal formulations. Quercetin is the major polyphenolic flavonoid found in food products, including berries, apples, cauliflower, tea, cabbage, nuts, and onions that have traditionally been treated as anticancer and antiviral, and used for the treatment of allergic, metabolic, and inflammatory disorders, eye and cardiovascular diseases, and arthritis. Pharmacologically, quercetin has been examined against various microorganisms and parasites, including pathogenic bacteria, viruses, and Plasmodium, Babesia, and Theileria parasites. Additionally, it has shown beneficial effects against Alzheimer’s disease (AD), and this activity is due to its inhibitory effect against acetylcholinesterase. It has also been documented to possess antioxidant, antifungal, anti-carcinogenic, hepatoprotective, and cytotoxic activity. Quercetin has been documented to accumulate in the lungs, liver, kidneys, and small intestines, with lower levels seen in the brain, heart, and spleen, and it is extracted through the renal, fecal, and respiratory systems. The current review examines the pharmacokinetics, as well as the toxic and biological activities of quercetin.

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16The association between adipose tissue and immunity has been established, and fat-associated 17 lymphoid clusters (FALCs) are considered a source of immune cells. We discovered lymphoid 18 clusters (LCs) in mouse mediastinal fat tissues (MFTs). In three mice strains, including Th1-biased ages. This is the first report of LCs in mouse MFTs and we suggest that the size and number of LCs 31 are affected by the mouse genetic background. We termed the LCs mediastinal fat-associated 32 lymphoid clusters (MFALCs). These clusters may be considered niches for Th cell production. 33 3

Aging is an oxidative stress-associated process that progresses with age. Our aim is to delay or attenuate these oxidative alterations and to keep individuals healthy as they age using natural compounds supplementation. Therefore, we conducted the present study to investigate the protective potentials of quercetin against D-galactose (D-gal)-associated oxidative alterations that were induced experimentally in male Wistar rats. Forty-five rats were randomly allocated into five groups of nine rats each. The groups were a control group that was reared on a basal diet and injected subcutaneously with 120 mg D-gal dissolved in physiological saline solution (0.9% NaCl) per kg body weight daily and quercetin-treated groups that received the same basal diet and subcutaneous daily D-gal injections were supplemented orally with 25, 50, and 100 mg of quercetin per kg body weight for 42 days. Pancreatic and renal samples were subjected to histopathological, immunohistochemical, and relative mRNA expression assessments. Aging (p53, p21, IL-6, and IL-8), apoptotic (Bax, CASP-3, and caspase-3 protein), proliferative (Ki67 protein), antiapoptotic (Bcl2 and Bcl2 protein), inflammatory (NF-κB, IL-1β, and TNF-α), antioxidant (SOD1), and functional markers (GCLC and GCLM genes and insulin, glucagon, and podocin proteins) were determined to evaluate the oxidative alterations induced by D-gal and the protective role of quercetin. D-gal caused oxidative alterations of the pancreas and kidneys observed via upregulations of aging, apoptotic, and inflammatory markers and downregulated the antiapoptotic, proliferative, antioxidant, and functional markers. Quercetin potentially attenuated these aging-related oxidative alterations in a dose-dependent manner. Finally, we can conclude that quercetin supplementation is considered as a promising natural protective compound that could be used to delay the aging process and to maintain human health.

Uncaria tomentosa (Willd. ex Schult.) DC. (Family: Rubiaceae), commonly known as cat’s claw, is a tropical medicinal vine originating at the Amazon rainforest and other areas of South and Central America. It has been traditionally used to treat asthma, abscesses, fever, urinary tract infections, viral infections, and wounds and found to be effective as an immune system rejuvenator, antioxidant, antimicrobial, and anti-inflammatory agent. U. tomentosa is rich in many phytoconstituents such as oxindole and indole alkaloids, glycosides, organic acids, proanthocyanidins, sterols, and triterpenes. Biological activities of U. tomentosa have been examined against various microorganisms and parasites, including pathogenic bacteria, viruses, and Plasmodium, Babesia and Theileria parasites. Several formulations of cat’s claw (e.g., tinctures, decoctions, capsules, extracts, and teas) are recently available in the market. The current review covers the chemical constituents, biological activities, pharmacokinetics, and toxic properties of U. tomentosa extracts.

Bleomycin (BLM) has been reported to induce lung inflammation and fibrosis in human and mice and showed genetic susceptibility. Interestingly, the C57BL/6 (B6) mice had prominent mediastinal fat-associated lymphoid cluster (MFALCs) under healthy condition, and showed susceptibility to development of lung fibrosis following BLM administration. However, the pathogenesis of lung lesion progression, and their correlation with MFALC morphologies, remain to be clarified. To investigate the correlations between MFALC structures and lung injuries in B6 mice, histopathological examination of mediastinal fat tissues and lungs was examined at 7 and 21 days (d) following a single 50 μL intranasal (i.n.) instillation of either BLM sulfate (5 mg/kg) (BLM group) or phosphate-buffered saline (control group). The lung fibrosis was examined by Masson’s trichrome (MT) stain of paraffin sections and mRNA expression levels of Col1a1, Col3a1, and Acta2 in different frozen lung samples. Furthermore, immunohistochemistry for CD3, B220, Iba1, Gr1, BrdU, LYVE-1, and peripheral node addressin (PNAd) was performed to detect T- and B-cells, macrophages, granulocytes, proliferating cells, lymph vessels (LVs), and high endothelial venules (HEVs). We found that MFALCs were more abundant in the BLM group as compared to the control group. The lung of BLM group developed pneumonitis with severe cellular infiltrations at 7 days and significant collagen deposition (MT) and higher expression of Col1a1, and Col3a1 at 21 days post-administration. Numerous immune cells, proliferating cells, HEVs, and LVs were observed in both MFALCs and lungs of the BLM group. Interestingly, PNAd + HEVs were observed in the lungs of the BLM group, but not the control group. Moreover, numerous Gr1 + polymorphonuclear and mononuclear-like ring cells were found in the MFALCs and lungs of the BLM group. Interestingly, flow cytometric analysis revealed a significant increase of B-cell populations within the MFALCs of BLM group suggesting a potential proliferative induction of B-cells following inflammation. Furthermore, significant positive correlations were observed between quantitative parameters of these immune cells in both the lungs and MFALCs. Thus, we suggest a potentially important role for MFALCs and HEVs in the progression of lung disease, especially in inflammatory lung disease.

The development of efficient gene delivery systems targeting the lung endothelium remains a serious challenge. This study reports on the design and optimization of a multifunctional envelope‐type nanodevice (MEND) for an efficient siRNA delivery to the lung endothelium based on GALA‐peptide targeting ability. The incorporation of a pH‐sensitive lipid (YSK05) results in a dramatic improvement in silencing efficiency by enhancing endosomal escape, but this also causes a reduction in the lung selectivity. Contrary to the assumption that active targeting is largely dependent on the presence of a targeting ligand, the findings of the present study indicate that nanocarrier composition is critical for achieving the organ selectivity. Interestingly, helper lipids substantially mask the liver delivery resulting in optimum lung targeting. The optimized YSK05‐MEND is 40‐fold more efficient than a previously developed MEND, with a robust lung endothelium gene knockdown at small doses. The YSK05‐MEND strongly inhibits a metastatic lung cancer model and exerts superior control over lung metastasis compared to chemotherapy or the previously developed MEND. The YSK05‐MEND is well‐tolerated in mice after acute or chronic administration. As far as it is known, YSK05‐MEND achieves the most efficient lung endothelium gene silencing reported thus far with a median effective dose of 0.01 mg siRNA kg−1 while minimally affecting the endothelium of other organs.