A Development Strategy of Tailor-made Natural Deep Eutectic Solvents for the Enhanced Extraction of Hydroxynaphthoquinones from Alkanna tinctoria Roots

Natural hydroxynaphthoquinone enantiomers (HNQs) are well-described pharmaceutical and cosmeceutical agents especially present in the roots of Alkanna tinctoria (L.) Tausch, a species native to the Mediterranean region. In this work, eco-friendly natural deep eutectic solvents (NaDESs) were developed for the selective extraction of these compounds. An extensive screening was performed using more than sixty tailor-made NaDESs. The impact of the intrinsic physicochemical properties on the HNQs extraction efficiency as well as the specificity towards the different enantiomeric pairs was thoroughly investigated. As a result of a multivariate analysis and of the one factor-a-time solvent optimization, the eutectic mixture composed of levulinic acid and glucose (LeG) using a molar ratio of 5:1 (molHBA:molHBD) and 20% of water (w/w) was found as the most appropriate mixture for the highest extraction efficiency of HNQs. Further optimization of the extraction process was attained by response surface methodology, using a temperature of 45 °C, a solid-to-liquid ratio of 30 mg/mL, and an extraction time of 50 min. A maximum extraction output of 41.72 ± 1.04 mg/g was reached for HNQs, comparable to that of the commonly used organic solvents. A solid-phase extraction step was also proposed for the recovery of HNQs and for NaDESs recycling. Our results revealed NaDESs as a highly customizable class of green solvents with remarkable capabilities for the extraction of HNQs.

Cytochalasan Alkaloids as TRAIL Sensitizers from an Endophytic Fungus Chaetomium sp.

Two new cytochalasans with a rare 6/6/5/5/7 pentacyclic ring system, named chaetoconvosins C−D (1−2), together with two known congeners (3−4), were isolated from the fermentation of an endophytic fungus, Chaetomium sp. SG-01, harbored in the fibrous roots of Schisandra glaucescens Diels. Their structures including the absolute configuration were elucidated by extensive spectroscopic (HRESIMS, NMR, and ECD) and X-ray crystallographic analyses. The TRAIL sensitivity of 1–4 in a TRAIL-resistant HT29 colorectal cancer cell line was evaluated, which revealed that co-treatment of 1–4 at 50 µM with TRAIL (150 ng/mL) reduced the HT29 cell viability by 19.0%, 24.1%, 17.9%, and 15.5%, respectively, compared to treatment with 1–4 alone.

Antimicrobial Formulation of Chrysopogon zizanioides Essential Oil in an Emulsified Lotion for Acne

Acne is a skin condition arising from excess sebum production and microbial overgrowth within the pilosebaceous unit. Several commercial essential oils have shown promising activity against acne-related pathogens. Due to their volatility and thermal instability, the formulation of essential oils into commercial products remains a pharmaceutical challenge. Thus, this study aimed to develop a viable anti-acne topical treatment as an oil-in-water emulsified lotion to overcome these challenges. Chrysopogon zizanioides (vetiver) displayed noteworthy antimicrobial activity with a mean minimum inhibitory concentration of 0.14 mg/mL against Cutibacterium acnes, Staphylococcus aureus, Staphylococcus epidermidis, and Streptococcus pyogenes. Emulsified lotions containing C. zizanioides were developed through the hydrophilic-lipophilic balance approach. At tested hydrophilic-lipophilic balance values of 8, 9, and 10, C. zizanioides emulsified lotions displayed maximum stability at hydrophilic-lipophilic balance 9 with a minimum change in mean droplet size and polydispersity index of 20.61 and 33.33%, respectively, over 84 days. The C. zizanioides emulsified lotion at optimum hydrophilic-lipophilic balance 9 completely inhibited the growth of C. acnes and killed S. aureus, S. epidermidis, and S. pyogenes within 24 h. Additionally, the lotion retained antimicrobial activity against these test micro-organisms over the 84-day stability test period. Thus, the C. zizanioides emulsified lotion demonstrated physical stability and antimicrobial efficiency, making it an ideal natural product anti-acne treatment.

Natural prenylated xanthones as potential inhibitors of PI3k/Akt/mTOR pathway in triple negative breast cancer cells

Three prenylated xanthones, garcinone E (1), bannaxanthone D (2) and bannanxanthone E (3) were isolated from the leaves of Garcinia mckeaniana Graib. Their structures were elucidated by spectral methods and compared with literature data. To evaluate their anti-proliferative effects in tumor cells, firstly, cisplatin was used as a positive control and the effects of compound 1-3 were determined by performing MTT assay in MDA-MB-231, CNE-2 and A549 cancer cells. The results showed compound 1-3 exhibited stronger inhibitory effect than cisplatin in MDA-MB-231. Further effects of compound 1-3 in TNBC MDA-MB-231 and MDA-MB-468 cells were examined by performing cell cycle and apoptosis assays. The results indicated that compound 1-3 had ability to arrest cell cycle at G2/M phase and induce apoptosis. Furthermore, compound 2 significantly down-regulated PI3K, Akt and mTOR levels in both total proteins and phosphorylated form, which is its potential anti-cancer mechanism. These findings indicated that those prenylated xanthones might serve as promising leading compounds for the development of anticancer drug for TNBC.

Anti-inflammatory Constituents from Caulis Trachelospermi

Caulis Trachelospermi, the stems with leaves of Trachelospermum jasminoides, is a well-known herbal drug of the Apocynaceae family recorded in the Chinese pharmacopeia and used for the treatment of inflammation-related diseases by ethnic minorities of China. The mechanism of anti-inflammatory activity and responsible constituents of T. jasminoides have not been well elucidated in previous studies. Preliminary investigation showed that both the water and the ethyl ester extracts of T. jasminoides exhibited potent inhibitory activity on nitric oxide (NO) production using lipopolysaccharide (LPS)-stimulated murine macrophages. Phytochemical investigation on these extracts afforded 23 compounds, including three new compounds (1 –3) identified on the basis of spectroscopic and mass spectrometric data. Anti-inflammatory bioassay showed that compounds 17, 18, 22, and 23 inhibited significantly the production of NO in a concentration-dependent manner. Further studies indicated that compound 23 inhibited significantly TNF-α and IL-6 produced by LPS-stimulated RAW 264.7 cells with good selectivity, as well as protein expression of iNOS in RAW 264.7 cells. These chemical constituents may contribute to the anti-inflammatory potential of T. jasminoides.

Microbiological and clinical effects of a Proanthocyanidin-enriched extract from Rumex acetosa in periodontally healthy carriers of Porphyromonas gingivalis

Rumex acetosa significantly inhibits the adhesion of Porphyromonas gingivalis (P.g.) to eukaryotic host cells in vitro. The objective of this randomized placebo-controlled pilot-trial was to analyze effects of a mouth rinse containing 0.8 % (w/w) of a quantified proanthocyanidin-enriched extract from Rumex acetosa (RA1) on microbiological, clinical, and cytological parameters in systemically healthy individuals without history of periodontitis, harboring P.g. intraorally. 35 subjects received a supragingival debridement (SD) followed by mouth rinsing (3 times daily) with either RA1 mouth rinse solution (test) or placebo (control) for 7 days as adjunct to routine oral hygiene. Supragingival biofilm samples were taken at screening visit, baseline (BL), 2, 4, 7 and 14 days after SD. P.g. and 11 other oral microorganisms were detected and quantified by rtPCR. Changes in the oral microbiota composition of one test and one control subject were assessed via high throughput 16S rRNS gene amplicon sequencing. Approximal Plaque Index (API) and the modified Sulcular Bleeding Index (SBI) were assessed at BL, 7- and 14-days following SD. Brush biopsies were taken at BL and 14 d following SD. Intergroup comparisons revealed no significant microbiological, cytological, and clinical differences at any timepoint. However, a significant reduction in SBI at day 14 (p=0.003) and API at day 7 (p=0.02) and day 14 (p=0.009) was found in the test group by intragroup comparison. No severe adverse events were observed. The results indicate that RA1 mouth rinse is safe but does not seem to inhibit colonization of P.g. or improve periodontal health following SD.

Cyclooxygenase Enzyme and Lipid Peroxidation Inhibitory Terpenoids and Steroidal compounds as Major Constituents in Cleome viscosa Leaves

Bioassay guided study of Cleome viscosa Linn. (Cleomaceae) leaves led to the isolation of a new cembrenoid diterpene (1) and three known compounds (2-4) from the hexane extract. The chemical structures of these compounds were elucidated by spectroscopic methods such as NMR (1D and 2D), HRMS and IR and identified and afforded compound 1, malabaric acid (2), stigmast-4-en-3-one (3) and stigmast-4-ene-3,6-dione (4). This is the first report of compounds 1 and 2 from C. viscosa Linn. Isolates were evaluated for anti-inflammatory activity using in vitro cyclooxygenase enzyme (COX-1 and -2) inhibitory assays. The novel cembrenoid diterpene (1) exhibited IC50 values of 8.4 μM for COX-1 enzyme and 45.2 μM for COX-2 enzyme, respectively. Similarly, malabaric acid (2) exhibited IC50 values of 11.5 μM for COX-1 enzyme and 46.9 μM for COX-2 enzyme, respectively. Their inhibitory activities were in par with non-steroidal anti-inflammatory drugs aspirin, ibuprofen and naproxen. Sterols 3 and 4 gave IC50 values of 62.6 and 67.9 μM, respectively for COX-1 enzyme while indicating weak COX-2 enzyme inhibition. Lipid peroxidation inhibitory (LPO) and MTT assays were used to determine antioxidant activity of these compounds. Compounds 1-4 showed LPO inhibition with IC50 values between 82 and 100 µM and moderate antioxidant activity in the MTT assay. Biological activities reported for these compounds are for the first time and it support anecdotal medicinal claims of C. viscosa Linn. leaves.

Undescribed C-Glycosylflavones from Corn Silk and Potential Anti-inflammatory Activity Evaluation of Isolates

Phytochemical investigation of corn silk resulted in isolation and characterization of four flavone C-glycosides, chrysoeriol 6-C-β-oliopyranosyl-7-O-β-D-glucopyranoside (1), 3′-methoxycassiaoccidentalin A (2), chrysoeriol 6-C-β-boivinopyranosyl-7-O-β-D-glucopyranoside (3), and ax-4"-OH-3′-methoxymaysin (4), a triterpenoid, friedelin (5), two sterols, (22E)-5,8-epidioxyergosta-6,22-dien-3β-ol (6) and 6β-hydroxystigmasta-4,22-diene-3-one (7), and a mixture of β-sitosterol and stigmasterol. Compounds 1 and 2 were previously undescribed. Structure elucidation of the isolated compounds was attained using spectral data including 1D and 2D NMR and HRESIMS. Compounds 1, 2, 5, and 6 inhibited iNOS activity in LPS-induced macrophages and decreased nitrite levels by 68.64+4.46, 65.67 + 6.47, 88.50 + 0.50, and 94.00 + 4.00 %, respectively, at 50 µM. Compound 5 also showed inhibition of NF-κB (51.00+1.50 %). Compounds 1 and 2 induced NAG-1 activity in chondrocytes by 1.80 + 0.05 and 2.00 + 0.13 fold, respectively. The extract of corn silk, however, did not exhibit inhibition of iNOS or NF-κB but induced NAG-1 by 1.80+ 0.51 fold.

Chemical principles of Boophone, Nerine, Crossyne, Clivia, Cryptostephanus, Haemanthus and Scadoxus of the South African Amaryllidaceae and their biological properties

The Amaryllidaceae features prominently amongst bulbous flowering plant families. Accommodating about a third of its species, South Africa affords a sound basis for Amaryllidaceae plant research. Boophone, Nerine, Crossyne, Clivia, Cryptostephanus, Haemanthus and Scadoxus have been well-represented in such endeavors. The account herein summarizes the studies undertaken between 2013-2020 on these genera in regards to their chemical and biological characteristics. A total of 136 compounds comprising 63 alkaloids and 73 non-alkaloid entities were described during this period from eighteen members of the title genera. The alkaloids were reflective of the structural diversity found in eight isoquinoline alkaloid groups of the Amaryllidaceae. Of these, the crinane (29 compounds), lycorane and homolycorine (11 compounds each) groups were the most-represented. The non-alkaloid substances were embracive of the same number of unrelated groups including, acids, phenolics, flavonoids and triterpenoids. A wide variety of assays were engaged to ascertain the biological activities of the isolated compounds, notably in regards to cancer and motorneuron-related diseases. There were also attempts made to determine the antimicrobial, anti-inflammatory and antioxidant effects of some of the substances. New information has also emerged on the herbicidal, insecticidal and plant growth regulatory effects of selected alkaloid principles. Coupled to the biological screening measures were in instances probes made to establish the molecular basis to some of the activities, particularly in relation to cancer and Parkinsonʹs disease.