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Phytochemical analysis of the twigs and leaves of Croton kinondoensis , endemic to Kenya, yielded known compounds 3-(3',4'-dimethoxyphenyl)-prop-1-ene ( 1) , 3-(3',4'-dimethoxyphenyl)-propenal ( 2 ), lupeol ( 3 ) and ent -trachyloban-19-oic acid ( 4 ), and a tentatively new ent -clerodane diterpenoid, crotokinondoenolide ( 5 ). ent -Trachy-loban-19-oic acid ( 4 ) showed good activity against a panel of drug-resistant strains of Staphylococcus aureus and Enterococcus spp with MIC -values of 25  µ g/mL.

Reported herein is an anti-HIV monochlorinated compound, 1β-acetoxy-3β-chloro-5α,6α-dihydroxycrotocascarin L ( 1 ), of the rare crotofolane diterpenoid class. Compound 1 , a suspected artifact of extraction, along with the previously undescribed 11β-acetoxycrotocascarin L ( 2 ) and a known compound, crotocascarin K ( 3 ), were isolated from the bark of Croton megalocarpus , a Kenyan oil-producing seed crop. Compounds 1 and 3 inhibited HIV-1 replication with IC 50 values of 28 and 5.5 nM, respectively. Furthermore, both compounds lacked cytotoxicity toward MT-4 cells and FM-55-M1 cells at concentrations of up to 50 μM. Compounds 1 and 3 were both found to inhibit HIV-1 protease.

An aromatic alkaloid-rich 'absolute' extract from Vepris gossweileri inhibited Saccharomyces cerevisiae at 62.5 μg.mL -1 and Bacillus subtilis at 500 μg.mL -1 . A loss of activity upon fractionation indicated possible synergistic effects. Three new acridones, gossweicridone A ( 3 ), B ( 4 ) and C ( 5 ) and known compounds from the extract were inactive. Combinations of compounds showed that a sub-fraction containing mixtures of minor compounds with ( Ε )-caryophyllene augmented activity by 50-folds, with MIC values of 19.6 μg.mL -1 for S. cerevisiae and 375.0 μg.mL -1 for B. subtilis , demonstrating potent ΣFIC values of 0.02 and 0.375 respectively. From the active sub-fraction, three compounds were assigned as tecleanatalensine B, 13 S -hydroxy-9 Z ,11 E ,15 E -octadecatrienoic acid and normelicopine. In combination with ( Ε )-caryophyllene they separately demonstrated MIC values of 18 μg.mL -1 , 34 μg.mL -1 and 16 μg.mL -1 , respectively against S. cerevisiae . The synergistic combinations were more potent with addition of pheophytin A, suggesting that the synergistic antifungal effect of the extract is multi-layered.

In our continued study on the anti-HIV activity of compounds present in CareVid TM , we report the HIV-1 integrase ((HIV-1 IN) inhibitory effects of pellitorine ( 1 ), oleuropein ( 2 ), magnoflorine ( 3 ), crotepoxide ( 4 ), ent -kaurane-16β,17-diol ( 5 ), crotocorylifuran ( 6 ), lupeol ( 7 ), betulin ( 8 ), and ellagic acid ( 9 ) in an in vitro enzyme assay, and in an in silico study. Ellagic acid, pellitorine, lupeol, and betulin showed an in vitro percentage inhibition against HIV-1 IN of 21.1%, 19.0%, 18.5%, and 16.8%, respectively, at a standard concentration of 25 μg/mL. However, from a pharmacokinetic perspective, ellagic acid has poor bioavailability, due to rapid elimination in metabolism in the gut microbiome. It was postulated that known gut catabolites of ellagic acid, urolithin A ( 10 ) and urolithin B ( 11 ) could be more promising candidates in exploring the anti-HIV activity of ellagic acid-rich medicinal species consumed orally. On the contrary, urolithin A and urolithin B demonstrated lower activity with comparison to ellagic acid. The binding affinity of compounds 1 - 9 , urolithin A, and urolithin B against the catalytic domain of HIV-1 IN was also explored by in silico methods. Docking studies showed oleuropein as the best candidate, with a predicted energy of binding of ΔG -5.81 kcal/mol, while ellagic acid showed moderate predicted inhibition (ΔG -4.38 kcal/mol) caused by the interaction between the carbonyl and the key Mg 2+ ion in the active site.

The chemistry of essential oils from the leaves of three African species of Croton ( C. gratissimus , C. pseudopulchellus and C. sylvaticus ) is comprehensively characterised. Two new volatile diterpenes were isolated from C. gratissimus and the structures assigned using 1D and 2D NMR. One is a furanyl-halimane methyl ester ( 1 ) assigned as 12-β-furanyl-halima-5,9-dien-4-methylcarboxylate (gratissihalimanoic ester); the other is an abietane ketone ( 2 ) assigned as ent -abiet-8(14), 13(15)-dien-3-one, which we have named gratissimone. High relative abundance of diterpenes in a hydrodistilled essential oil is rare and may be considered an interesting discovery. Known non-volatile diterpenes were also isolated, which were assigned as crotohalimaneic acid ( 3 ) and hardwickiic acid ( 4 ). All diterpenes occur in fresh leaves prior to distillation and extract into apolar or moderately polar solvents, which demonstrates that the two volatiles are not generated during the hydrodistillation. At this stage it is not clear how widespread this diterpene essential oil chemotype is within the species distribution or if any therapeutic effects can be attributed to them. No antimicrobial activity was observed at 1 mg/ml against a range of bacterial strains., (© 2019 Published by Elsevier Ltd.)

Ethnopharmacological Relevance: The twigs of Elytropappus rhinocerotis are widely used in the Cape region of South Africa to treat foot odour, perspiration and also itchy, chilblained and burning feet. However, no antimicrobial studies have hitherto been published on this popular Cape herbal medicine, which is also used for a wide range of ailments., Aims of the Study: To determine the antimicrobial activity of the extracts, essential oil and two major labdane diterpenes isolated from E. rhinocerotis against micro-organisms associated with foot odour and other conditions associated with skin infections., Materials and Methods: Leafy stems were harvested from three individual plants at three separate geographical localities, giving a total of nine plant samples. The samples were air-dried, powdered and extracted with a 1:1 mixture of methanol and dichloromethane, and also with sterile distilled water. A portion of each sample was also hydrodistilled to obtain nine samples of essential oil. Isolation of the major labdane diterpenes was performed using silica and ethyl acetate in hexane (3:7 v/v) as the mobile phase. Minimum inhibitory concentrations (MIC) were determined for nine crude extracts, as well as three essential oil samples and two labdane diterpenes obtained from a bulk sample. The test organisms used in this study were from Deutsche Sammlung von Mikrooganismen (DSM) and American type culture collection (ATCC) strains and included five bacterial species (Brevibacterium agri ATCC 51663, B. epidermidis DSM 20660, B. linens DSM 20425, Staphylococcus aureus ATCC 25923, S. epidermidis ATCC 12228) and one fungal species (Trichophyton mentagrophytes ATCC 9533) associated with the skin., Results: The presence of essential oil is reported for the first time. Organic extracts and essential oil samples showed moderate to noteworthy activity against selected test organisms. For the Brevibacteria, the lowest MIC values for phenolic extracts were several times lower than the corresponding values for the positive control zinc (shown in brackets): 0.0031 mg/mL against Brevibacterium agri (0.33 mg/mL), 0.17 mg/mL against B. epidermidis (3.91 mg/mL) - both for sample 2 of Vanwyksdorp; 0.13 mg/mL against B. linens (2.28 mg/mL) - for sample 3 of Vanwyksdorp. Two isolated labdane diterpenoids (one of which is here first reported) were also antimicrobially tested and showed moderate activity but had high abundance in the extracts. Two major monoterpenes and four sesquiterpenes in the essential oil were identified as 1,8-cineole (4.6-12.3%), terpinen-4-ol (9.2-24.3%), germacrene A (3.9-15.6%), (-)-spathulenol (1.7-37.8%), viridiflorol (0.3-100%), and silphiperfol-6-en-5-one (4.5-26.8%)., Conclusion: The antimicrobial results particularly for the essential oils and against the Brevibacteria support the traditional topical use of Elytropappus rhinocerotis twigs to treat foot perspiration, foot odour and other related skin conditions., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Ethnopharmacological Significance: Eremophila longifolia is one of the most respected of the traditional medicines used by Australian Aboriginal people. Customary use involves smoldering the leaves over hot embers of a fire to produce an acrid smoke, believed to have therapeutic effects broadly consistent with antimicrobial, antifungal and anti-inflammatory capacity., Aim of the Study: The current study aims to examine the contribution of partially pyrolysed and non-pyrolysed essential oils in traditional usage of Eremophila longifolia., Materials and Methods: Non-pyrolysed and partially pyrolysed essential oils were produced by hydrodistillation and part-wet/part-dry distillation, respectively. All samples were tested for antimicrobial activity by broth dilution. Some of these samples were further treated to an incrementally stepped temperature profile in a novel procedure employing a commercial thermocycler in an attempt to mimic the effect of temperature gradients produced during smoking ceremonies. Components from the pyrodistilled oils were compared with the non-pyrodistilled oils, using GC-MS, GC-FID and HPLC-PAD. The 2,2-diphenyl-1-picrylhydrazyl method, was used to compare free radical scavenging ability., Results: Partially pyrolysed oils had approximately three or more times greater antimicrobial activity, enhanced in cultures warmed incrementally to 60°C and held for 30s and further enhanced if held for 2 min. Partially pyrolysed oils showed a radical scavenging capacity 30-700 times greater than the corresponding non-pyrolysed oils. HPLC-PAD revealed the presence of additional constituents not present in the fresh essential oil., Conclusion: These results, by showing enhanced antimicrobial and antioxidant activities, provide the first known Western scientific justification for the smoking ceremonies involving leaves of Eremophila longifolia. During customary use, both partially pyrolysed as well as non-pyrolysed essential oils may contribute significantly to the overall intended medicinal effect., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)