Real-World, Open-Label Study of the Efficacy and Safety of a Novel Serum in Androgenetic Alopecia.

Pattern-type hair loss is a highly prevalent condition affecting the majority of men and women at some point in their lifetime. Although genetics and androgens are instrumental in the pathogenesis of this type of hair loss, it is increasingly recognized that inflammation, stress, and environmental factors play a central role. The few and widely used monotherapies approved by the US Food and Drug Administration, such as minoxidil or finasteride, are not efficacious in all people and cause adverse events that prevent patient compliance. Therefore, new treatments that are easy to use and that holistically address the multi-factorial pathophysiology of pattern-type hair loss are needed. Clinical studies have already demonstrated the safety and efficacy of a plethora of bioactive natural products, such as epigallocatechin gallate (EGCG), Vitis vinifera seed extract, Glycyrrhiza root extract, apigenin, and saw palmetto extract to name a few, in improving hair follicle homeostasis via anti-inflammatory, anti-androgen, anti-microbial, and anti-oxidant action. Here, we present a novel topical serum, REVIVV®, that contains a proprietary blend of phytochemicals designed to stimulate hair growth, reduce shedding, and restore homeostasis to the hair follicle. The serum’s safety and efficacy were assessed in 150 participants in a real-world clinical setting. Findings demonstrate that twice-daily use of the serum significantly improves hair growth, and reduces shedding after 8 weeks of use. All participants rated the serum as easy to use and stated plans for continued use. Overall, the topical serum REVIVV® showed evidence of good efficacy related to hair growth and had positive cosmetic properties warranting further evaluation in clinical studies. Rapaport J, Sadgrove NJ, Arruda S, et al. Real-world, open-label study of the efficacy and safety of a novel serum in androgenetic alopecia. J Drugs Dermatol. 2023;22(6):559-564. doi:10.36849/JDD.7403.

Medicinal plants used by rural Thai people to treat non-communicable diseases and related symptoms.

Non-communicable diseases (NCDs) are becoming more common in remote regions, whereas previously they were more common in middle-class to wealthy societies. The rising prevalence and severity of NCDs has increased the demand for medical innovation in this space. In this regard, knowledge of traditional medicines used in the treatment of NCDs, by people in the remote communities of Thailand, represents an innovation opportunity. This study aims to use data on ethnomedicinal plants used by local Thai people to identify plant candidates for study of safety and efficacy against a range of specified NCDs. Data were taken from both the literature and interviews from 230 locations in Thailand. The consulted literature was published in the years from 1990 to 2020. Ethnomedicinal field observations were made in person, in villages in Nan and Chiang Rai provinces, in 2021. Data includes names of plants used to target NCDs, and names of target diseases. Important plant species were identified based on the number of use reports and use values together with results from Bayesian approach. A total of 766 plant species were recorded in the treatment of NCDs. Most of the species that were described by informants were used to target diabetes, hypertension, chronic respiratory and renal diseases. This study proposes several plant species that have potential as treatments against NCDs. Many of these important species have insufficient scientific data to support their uses. The study suggests that assessment of efficacy and safety should be the next logical steps.

Rumors of Psychedelics, Psychotropics and Related Derivatives in Vachellia and Senegalia in Contrast with Verified Records in Australian Acacia.

There are almost 1000 species of Acacia sensu stricto in Australia, while the 44 species and 4 subspecies in southern Africa were taxonomically revised in the year 2011 to Senegalia and Vachellia. There are rumors of a chemical similarity between the Australian Acacia and their southern African sister genera. Chemical analysis has unequivocally demonstrated the presence of tryptamines (i.e., DMT), ß-carbolines, histamines, and phenethylamines in Australian species. However, reliable published data were not found in support of similar alkaloids in southern African (or even African) species, indicating the need for exploratory phytochemical analysis. Interestingly, the Australian species are more like the Vachellia and Senegalia from the Americas. While many reliable chemical studies have been found, there are several more that report only tentative results. Tentative data and anecdotal accounts are included in the current review to guide researchers to areas where further work can be done. For example, the current review encourages further phytochemical work to confirm if the two metabolite families, tryptamine and ß-carboline alkaloids, occur together in a single specimen. Tryptamines and ß-carbolines are the prerequisite ingredients of the South American psychotropic drink ayahuasca, which utilizes two different species to create this synergistic combination. These observations and others are discussed in light of geochemical variability, the potential ethnobotanical implications, and the need for further research to confirm or nullify anecdotal reports and tentative chromatographic/spectroscopic data in southern African species.

HIV-1 Integrase Inhibitory Effects of Major Compounds Present in CareVid™: An Anti-HIV Multi-Herbal Remedy.

In our continued study on the anti-HIV activity of compounds present in CareVidTM, we report the HIV-1 integrase ((HIV-1 IN) inhibitory effects of pellitorine (1), oleuropein (2), magnoflorine (3), crotepoxide (4), ent-kaurane-16ß,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 Mg2+ ion in the active site.

Honest nutraceuticals, cosmetics, therapies, and foods (NCTFs): standardization and safety of natural products.

With the increasing demand for natural products by the consumer in the marketplace it is necessary to see a proportional increase in behind-the-scenes science to ensure that the ideology of safety and honesty, that is justifiably expected by the wider public, is adequately satisfied. It is of essence to have a fair yet firm governance of nutraceuticals, cosmetics, therapies, and foods. However, with increasing sophistications in adulteration and "claim" loopholes that make it easier for adulterated or counterfeited natural products to be "fudged" to meet the pharmacopeia standards, governance protocols must utilize an "identification and authentication" approach that goes beyond the Pharmacopeia standards to help regulate and transparently communicate natural products in the commercial context. While it is becoming a rat race in keeping commercial natural products honest, modern technology can support authenticators and adequately defeat these challenges.

Multi-layered antimicrobial synergism of (E)-caryophyllene with minor compounds, tecleanatalensine B and normelicopine, from the leaves of Vepris gossweileri (I. Verd.) Mziray.

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, 13S-hydroxy-9Z,11E,15E-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.

Pharmacology of Natural Volatiles and Essential Oils in Food, Therapy, and Disease Prophylaxis.

This commentary critically examines the modern paradigm of natural volatiles in 'medical aromatherapy', first by explaining the semantics of natural volatiles in health, then by addressing chemophenetic challenges to authenticity or reproducibility, and finally by elaborating on pharmacokinetic and pharmacodynamic processes in food, therapy, and disease prophylaxis. Research over the last 50 years has generated substantial knowledge of the chemical diversity of volatiles, and their strengths and weaknesses as antimicrobial agents. However, due to modest in vitro outcomes, the emphasis has shifted toward the ability to synergise or potentiate non-volatile natural or pharmaceutical drugs, and to modulate gene expression by binding to the lipophilic domain of mammalian cell receptors. Because essential oils and natural volatiles are small and lipophilic, they demonstrate high skin penetrating abilities when suitably encapsulated, or if derived from a dietary item they bioaccumulate in fatty tissues in the body. In the skin or body, they may synergise or drive de novo therapeutic outcomes that range from anti-inflammatory effects through to insulin sensitisation, dermal rejuvenation, keratinocyte migration, upregulation of hair follicle bulb stem cells or complementation of anti-cancer therapies. Taking all this into consideration, volatile organic compounds should be examined as candidates for prophylaxis of cardiovascular disease. Considering the modern understanding of biology, the science of natural volatiles may need to be revisited in the context of health and nutrition.

HIV-1 Reverse Transcriptase Inhibition by Major Compounds in a Kenyan Multi-Herbal Composition (CareVid™): In Vitro and In Silico Contrast.

CareVid is a multi-herbal product used in southwest Kenya as an immune booster and health tonic and has been anecdotally described as improving the condition of HIV-positive patients. The product is made up of roots, barks and whole plant of 14 African medicinal plants: Acacia nilotica (L.) Willd. ex Delile (currently, Vachelia nilotica (L.) P.J.H Hurter & Mabb.), Adenia gummifera (Harv.) Harms, Anthocleista grandiflora Gilg, Asparagus africanus Lam., Bersama abyssinica Fresen., Clematis hirsuta Guill. & Perr., Croton macrostachyus Hochst. ex Delile, Clutia robusta Pax (accepted as Clutia kilimandscharica Engl.), Dovyalis abyssinica (A. Rich.) Warb, Ekebergia capensis Sparm., Periploca linearifolia Quart.-Dill. & A. Rich., Plantago palmata Hook.f., Prunus africana Hook.f. Kalkman and Rhamnus prinoides L'Her. The objective of this study was to determine the major chemical constituents of CareVid solvent extracts and screen them for in vitro and in silico activity against the HIV-1 reverse transcriptase enzyme. To achieve this, CareVid was separately extracted using CH2Cl2, MeOH, 80% EtOH in H2O, cold H2O, hot H2O and acidified H2O (pH 1.5-3.5). The extracts were analysed using HPLC-MS equipped with UV diode array detection. HIV-1 reverse transcriptase inhibition was performed in vitro and compared to in silico HIV-1 reverse transcriptase inhibition, with the latter carried out using MOE software, placing the docking on the hydrophobic pocket in the subdomain of p66, the NNRTI pocket. The MeOH and 80% EtOH extracts showed strong in vitro HIV-1 reverse transcriptase inhibition, with an EC50 of 7 µg·mL-1. The major components were identified as sucrose, citric acid, ellagic acid, catechin 3-hexoside, epicatechin 3-hexoside, procyanidin B, hesperetin O-rutinoside, pellitorine, mangiferin, isomangiferin, 4-O-coumaroulquinic acid, ellagic acid, ellagic acid O-pentoside, crotepoxide, oleuropein, magnoflorine, tremulacin and an isomer of dammarane tetrol. Ellagic acid and procyanidin B inhibited the HIV-1 reverse transcription process at 15 and 3.2 µg/mL-1, respectively. Docking studies did not agree with in vitro results because the best scoring ligand was crotepoxide (ΔG = -8.55 kcal/mol), followed by magnoflorine (ΔG = -8.39 kcal/mol). This study showed that CareVid has contrasting in vitro and in silico activity against HIV-1 reverse transcriptase. However, the strongest in vitro inhibitors were ellagic acid and procyanidin B.

Advanced Chemophenetic Analysis of Essential Oil from Leaves of Piper gaudichaudianum Kunth (Piperaceae) Using a New Reduction-Oxidation Index to Explore Seasonal and Circadian Rhythms.

The aromatic species Piper gaudichaudianum Kunth (Piperaceae) is widely used in Brazil for medicinal and ritualistic applications. In the current study, chemophenetic patterns were realized across season and circadian rhythm based on the chemical profile of essential oils (EOs) from leaves. Hydrodistilled essential oils were analyzed by GC-MS and GC-FID, and a new calculation of metabolite oxidation level, averaged for each individual molecule component of the EO, was used to explore the patterns of metabolism/biosynthesis. This new index used an intermediate calculation, the 'weighted average redox standard' (SRO), to enable a value for mixtures of metabolites to be generated, the 'general mixture redox index' (GMOR). The indices were subjected to a proof-of-concept approach by making comparison to outcomes from multivariate analyses, i.e., PCA and HCA. Chemical analysis demonstrated that the essential oils were dominated by sesquiterpenes, constructed of 15 classes of compound (C-skeletons), and 4 C-skeletons were recognized in the monoterpene group, giving a total of 19. The variation of chemical profiles was distinct at different phenological stages, but stronger chemical variation was evident between day and night as compared to season. Furthermore, due to comprehensive sampling across different regions, nine chemotypes were recognized, including those previously reported. The SRO and GMRO indices demonstrate that phenological variation of chemistry is mainly an outcome of redox fluctuations in terpene biosynthesis, changing from day to night. These indices also corroborate that chemical diversity is increased with oxidative metabolism. Lastly, the current study demonstrates pronounced phenotypic plasticity in P. gaudichaudianum, which makes it a suitable candidate to help further our understanding of chemophenetics and chemical ecology.

The Ethnobotany and Chemistry of South African Meliaceae: A Review.

Meliaceae are widely distributed across the world in tropical or subtropical climates and are of considerable ethnobotanical importance as sources of traditional medicine and cosmetics. This comprehensive review summarizes the ethnobotanical uses and chemistry of 12 South African species, belonging to six genera: Ekebergia, Nymania, Entandrophragma, Pseudobersama, Trichilia, and Turraea. Eight of the species have ethnomedicinal records, classified into 17 major disease categories. The ethnomedicinal uses comprise 85 ailments dominated by gastrointestinal complaints, followed by gynaecological and obstetrics related problems. Chemical records were found for 10 species, which describe nine classes of compounds. In nearly all South African Meliaceae, limonoids are the predominant constituents while triterpenes, sterols, and coumarins are also common. The widest range of use-records and medicinal applications are found with the two most chemically diverse species, Ekebergiacapensis and Trichiliaemetica. Of the chemical compounds identified in the various plant organs of the 10 species of South African Meliaceae for which data are available, 42% was found in bark and 17% in seeds. Roots represent 35% and bark 33% of the organs that are used medicinally, and they are typically prepared as decoctions or infusions. Root and bark harvesting are destructive so that it may be important to examine the chemistry of plant parts such as wild-crafted leaves and fruits.

Pharmacodynamics of Aloe vera and acemannan in therapeutic applications for skin, digestion, and immunomodulation.

Scientific studies of Aloe vera have tentatively explained therapeutic claims from a mechanistic perspective. Furthermore, in vitro outcomes demonstrate that the breakage of acemannan chains into smaller fragments enhances biological effects. These fragments can intravenously boost vaccine efficacy or entrain the immune system to attack cancer cells by mannose receptor agonism of macrophage or dendritic cells. With oral consumption, epithelialisation also occurs at injured sites in the small intestine or colon. The main advantage of dietary acemannan is the attenuation of the digestive process, increasing satiety, and slowing the release of sugars from starches. In the colon, acemannan is digested by microbes into short-chain fatty acids that are absorbed and augment the sensation of satiety and confer a host of other health benefits. In topical applications, an acemannan/chitosan combination accelerates the closure of wounds by promoting granular tissue formation, which creates a barrier between macrophages or neutrophils and the wound dressing. This causes M2 polarisation, reversal of inflammation, and acceleration of the re-epithelialisation process. This review summarises and explains the current pharmacodynamic paradigm in the context of acemannan in topical, oral, and intravenous applications. However, due to contradictory results in the literature, further research is required to provide scientific evidence to confirm or nullify these claims.

South Africa's Best BARK Medicines Prescribed at the Johannesburg Muthi Markets for Skin, Gut, and Lung Infections: MIC's and Brine Shrimp Lethality.

Indigenous trade of medicinal plants in South Africa is a multi-million-rand industry and is still highly relevant in terms of primary health care. The purpose of this study was to identify today's most traded medicinal barks, traditionally and contemporaneously used for dermatological, gastrointestinal, and respiratory tract infections; then, to investigate the antimicrobial activity and toxicity of the respective extracts and interpret outcomes in light of pharmacokinetics. Thirty-one popularly traded medicinal barks were purchased from the Faraday and Kwa Mai-Mai markets in Johannesburg, South Africa. Information on the medicinal uses of bark-based medicines in modern commerce was recorded from randomly selected traders. The minimum inhibitory concentration (MIC) method was used for antimicrobial screening, and brine shrimp lethality was used to determine toxicity. New medicinal uses were recorded for 14 bark species. Plants demonstrating some broad-spectrum activities against tested bacteria include Elaeodendron transvaalense, Erythrina lysistemon, Garcinia livingstonei, Pterocelastrus rostratus, Rapanea melanophloeos, Schotia brachypetala, Sclerocarya birrea, and Ziziphus mucronata. The lowest MIC value of 0.004 mg/mL was observed against Staphylococcus epidermidis for a dichloromethane bark extract of E. lysistemon. The tested medicinal barks were shown to be non-toxic against the Artemia nauplii (brine shrimp) bioassay, except for a methanol extract from Trichilia emetica (69.52% mortality). Bacterial inhibition of bark extracts with minimal associated toxicity is consistent with the safety and valuable use of medicinal barks for local muthi market customers. Antimicrobial outcomes against skin and gastrointestinal pathogens are feasible because mere contact-inhibition is required in vivo; however, MIC values against respiratory pathogens require further explaining from a pharmacokinetics or pharmacodynamics perspective, particularly for ingested rather than smoked therapies.

Potential chemopreventive, anticancer and anti-inflammatory properties of a refined artocarpin-rich wood extract of Artocarpus heterophyllus Lam.

Colorectal cancer (CRC) represents the third leading cause of death among cancer patients below the age of 50, necessitating improved treatment and prevention initiatives. A crude methanol extract from the wood pulp of Artocarpus heterophyllus was found to be the most bioactive among multiple others, and an enriched extract containing 84% (w/v) artocarpin (determined by HPLC-MS-DAD) was prepared. The enriched extract irreversibly inhibited the activity of human cytochrome P450 CYP2C9, an enzyme previously shown to be overexpressed in CRC models. In vitro evaluations on heterologously expressed microsomes, revealed irreversible inhibitory kinetics with an IC50 value of 0.46 µg/mL. Time- and concentration-dependent cytotoxicity was observed on human cancerous HCT116 cells with an IC50 value of 4.23 mg/L in 72 h. We then employed the azoxymethane (AOM)/dextran sodium sulfate (DSS) colitis-induced model in C57BL/6 mice, which revealed that the enriched extract suppressed tumor multiplicity, reduced the protein expression of proliferating cell nuclear antigen, and attenuated the gene expression of proinflammatory cytokines (Il-6 and Ifn-γ) and protumorigenic markers (Pcna, Axin2, Vegf, and Myc). The extract significantly (p = 0.03) attenuated (threefold) the gene expression of murine Cyp2c37, an enzyme homologous to the human CYP2C9 enzyme. These promising chemopreventive, cytotoxic, anticancer and anti-inflammatory responses, combined with an absence of toxicity, validate further evaluation of A. heterophyllus extract as a therapeutic agent.

Antimicrobial Isoflavones and Derivatives from Erythrina (Fabaceae): Structure Activity Perspective (Sar & Qsar) on Experimental and Mined Values Against Staphylococcus Aureus.

Prenylated (iso)flavonoids, -flavans and pterocarpans from taxa in Erythrina are repeatedly flagged as potent antimicrobial compounds. In the current study, bark from E. lysistemon was extracted and seven isoflavone derivatives were purified: erybraedin A (1), phaseollidin (2), abyssinone V-4' methyl ether (3), eryzerin C (4), alpumisoflavone (5), cristacarpin (6) and lysisteisoflavone (7). Minimum inhibition concentration (MIC) values were determined against a range of species of bacteria (skin pathogens), then values for another 67 derivatives from Erythrina, only against Staphylococcus aureus, were mined from the literature. Of the seven isolates, MIC values widely ranged from 1-600 µg/mL, with no obvious pattern of selectivity for Gram-types. Nevertheless, using the mined and experimentally determined values against S. aureus, Klekota-Roth fragments (Structure Activity Relationship: SAR) were determined then used as molecular descriptors to make a 'decision tree' based on structural characters inspired by the classes of antimicrobial potency (classes A-D). Furthermore, to make quantitative predictions of MIC values (Quantitative SAR: QSAR) 'pace regression' was utilized and validated (R² = 0.778, Q² = 0.727 and P² = 0.555). Evidently, the position and degree of prenylation is important; however, the presence of hydroxyl groups at positions 5 and 7 in ring A and 4' in ring B is associated with lower MIC values. While antimicrobial results continue to validate the traditional use of E. lysistemon extracts (or Erythrina generally) in therapeutic applications consistent with anti-infection, it is surprising that this class of compound is not being utilized more often in general industry applications, such as food or cosmetic preservation, or in topical antimicrobial creams. Prenylated (iso)flavonoids are derived from several other Genera, such as Dorstenia (Moraceae), Ficus (Moraceae), Glycyrrhiza (Fabaceae), Paulownia (Lamiales) or Pomifera (Moraceae).

High-Value Plant Species Used for the Treatment of "Fever" by the Karen Hill Tribe People.

The symptom "fever" is generally not itself a terminal condition. However, it does occur with common mild to severe ailments afflicting the world population. Several allopathic medicines are available to attenuate fever by targeting the pathogen or the symptom itself. However, many people in marginal civilizations are obligated to use locally grown medicinal plants due to limited access to common pharmaceuticals. The Karen ethnic group is the biggest ethnic minority group in the hill-tribes of Thailand. They utilise a vast repertoire of medicinal plant species. Since many modern drugs were discovered out of traditional therapies, it is possible to discover new allopathic drugs in the treatment of fever and associated pathogens from the Karen people. Thus, this study aims to identify and record the ethnomedicinal plants they used for the treatment of "fever". The names of plants used by the Thai Karen people for the treatment of fever were mined from publications on ethnomedicinal uses. Useful plant species and families were identified using the Cultural Importance Index (CI). With the mined data, 125 plant species from 52 families were identified, distributed across 25 Karen villages. A chemical cross-examination of these species provided valuable insights into chemical classes worthy of further investigation in the context of fever and associated pathogens.

New Labdanes with Antimicrobial and Acaricidal Activity: Terpenes of Callitris and Widdringtonia (Cupressaceae).

In spite of the evidence for antimicrobial and acaricidal effects in ethnobotanical reports of Callitris and Widdringtonia, the diterpene acids from Widdringtonia have never been described and no comparison to the Australian clade sister genus Callitris has been made. The critically endangered South African Clanwilliam cedar, Widdringtonia wallichii (syn. W. cedarbergensis), of the Cederberg Mountains was once prized for its enduring fragrant timbers and an essential oil that gives an aroma comparable to better known Mediterranean cedars, predominantly comprised by widdrol, cedrol, and thujopsene. In South Africa, two other 'cedars' are known, which are called W. nodiflora and W. schwarzii, but, until now, their chemical similarity to W. wallichii has not been investigated. Much like Widdringtonia, Callitris was once prized for its termite resistant timbers and an 'earthy' essential oil, but predominantly guaiol. The current study demonstrates that the essential oils were similar across all three species of Widdringtonia and two known non-volatile diterpene acids were identified in leaves: the pimaradiene sandaracopimaric acid (1) and the labdane Z-communic acid (2) with a lower yield of the E-isomer (3). Additionally, in the leaves of the three species, the structures of five new antimicrobial labdanes were assigned: 12-hydroxy-8R,17-epoxy-isocommunic acid (4), 8S-formyl-isocommunic acid (5), 8R,17-epoxy-isocommunic acid (6), 8R-17R-epoxy-E-communic acid (7), and 8R-17-epoxy-E-communic acid (8). Australian Callitris columellaris (syn. C. glaucophylla) also produced 1 and its isomer isopimaric acid, pisiferal (9), and pisiferic acid (10) from its leaves. Callitris endlicheri (Parl.) F.M.Bailey yielded isoozic acid (11) as the only major diterpene. Diterpenes 4-6, pisiferic acid (10), spathulenol, and guaiol (12) demonstrated antimicrobial and acaricidal activity.

From Petri Dish to Patient: Bioavailability Estimation and Mechanism of Action for Antimicrobial and Immunomodulatory Natural Products.

The new era of multidrug resistance of pathogens against frontline antibiotics has compromised the immense therapeutic gains of the 'golden age,' stimulating a resurgence in antimicrobial research focused on antimicrobial and immunomodulatory components of botanical, fungal or microbial origin. While much valuable information has been amassed on the potency of crude extracts and, indeed, purified compounds there are too many reports that uncritically extrapolate observed in vitro activity to presumed ingestive and/or topical therapeutic value, particularly in the discipline of ethnopharmacology. Thus, natural product researchers would benefit from a basic pharmacokinetic and pharmacodynamic understanding. Furthermore, therapeutic success of complex mixtures or single components derived therefrom is not always proportionate to their MIC values, since immunomodulation can be the dominant mechanism of action. Researchers often fail to acknowledge this, particularly when 'null' activity is observed. In this review we introduce the most up to date theories of oral and topical bioavailability including the metabolic processes affecting xenobiotic biotransformation before and after drugs reach the site of their action in the body. We briefly examine the common methodologies employed in antimicrobial, immunomodulatory and pharmacokinetic research. Importantly, we emphasize the contribution of synergies and/or antagonisms in complex mixtures as they affect absorptive processes in the body and sometimes potentiate activity. Strictly in the context of natural product research, it is important to acknowledge the potential for chemotypic variation within important medicinal plants. Furthermore, polar head space and rotatable bonds give a priori indications of the likelihood of bioavailability of active metabolites. Considering this and other relatively simple chemical insights, we hope to provide the basis for a more rigorous scientific assessment, enabling researchers to predict the likelihood that observed in vitro anti-infective activity will translate to in vivo outcomes in a therapeutic context. We give worked examples of tentative pharmacokinetic assessment of some well-known medicinal plants.

The new paradigm for androgenetic alopecia and plant-based folk remedies: 5α-reductase inhibition, reversal of secondary microinflammation and improving insulin resistance.

ETHNOPHARMACOLOGICAL RELEVANCE: Research in the past half a century has gradually sketched the biological mechanism leading to androgenetic alopecia (AGA). Until recently the aetiological paradigm has been too limited to enable intelligent commentary on the use of folk remedies to treat or reduce the expression of this condition. However, our understanding is now at a point where we can describe how some folk remedies work, predict how effective they will be or why they fail. RESULTS: The new paradigm of AGA is that inheritance and androgens (dihydrotestosterone) are the primary contributors and a secondary pathology, microinflammation, reinforces the process at more advanced stages of follicular miniaturisation. The main protagonist to microinflammation is believed to be microbial or Demodex over-colonisation of the infundibulum of the pilosebaceous unit, which can be ameliorated by antimicrobial/acaricidal or anti-inflammatory therapies that are used as adjuvants to androgen dependent treatments (either synthetic or natural). Furthermore, studies reveal that suboptimal androgen metabolism occurs in both AGA and insulin resistance (low SHBG or high DHT), suggesting comorbidity. Both can be ameliorated by dietary phytochemicals, such as specific classes of phenols (isoflavones, phenolic methoxy abietanes, hydroxylated anthraquinones) or polycyclic triterpenes (sterols, lupanes), by dual inhibition of key enzymes in AGA (5α-reductase) and insulin resistance (ie., DPP-4 or PTP1B) or agonism of nuclear receptors (PPARγ). Evidence strongly indicates that some plant-based folk remedies can ameliorate both primary and secondary aetiological factors in AGA and improve insulin resistance, or act merely as successful adjuvants to mainstream androgen dependent therapies. CONCLUSION: Thus, if AGA is viewed as an outcome of primary and secondary factors, then it is better that a 'multimodal' or 'umbrella' approach, to achieve cessation and/or reversal, is put into practice, using complementation of chemical species (isoflavones, anthraquinones, procyanidins, triterpenes, saponins and hydrogen sulphide prodrugs), thereby targeting multiple 'factors'.

The Iridoid Myodesert-1-ene and Elemol/Eudesmol are found in Distinct Chemotypes of the Australian Aboriginal Medicinal Plant Eremophila dalyana (Scrophulariaceae).

The strongly aromatic Australian desert species Eremophila dalyana is an Aboriginal medicinal plant that continues to be used today in Central Australia in the treatment of respiratory complaints and Sarcoptes scabiei infestation. Using hydrodistillation of aerial parts of the plant, the new natural product myodesert-l- ene was isolated in two disjunct populations at up to 98% of the volatiles present in the hydrodistilled oils. Weak antimicrobial activities were observed for whole oils and myodesert-l-ene. Activities in the hydrodistilled oil were attributed to the antimicrobial sesquiterpenes elemol and eudesmol which showed good activity when isolated and were relatively abundant in the chemotype used medicinally. The biogenesis of myodesert-l-ene from iridodial is proposed.

Chemogeography and antimicrobial activity of essential oils from Geijera parviflora and Geijera salicifolia (Rutaceae): two traditional Australian medicinal plants.

Essential oils were hydrodistilled from 27 specimens of Geijera parviflora Lindl., (Rutaceae) and nine specimens of Geijera salicifolia Schott, collected over a wide geographic range in New South Wales, Queensland and South Australia. Essential oils were produced by traditional hydrodistillation and characterised using GC-MS. From one specimen a serendipitous discovery was made of bioactive coumarins dissolved in the hydrosol, which were the coumarins isopsoralen, xanthyletine and osthole. These coumarins were not present in the essential oil from that specimen. Using essential oil composition from all specimens, principal component analysis (PCA) demonstrated nine clusters for G. parviflora and three for G. salicifolia. Some clusters are representative of previously described chemotypes and some are reflective of possible chemotypes requiring more comprehensive sampling for confirmation. Thus, another three or four possible chemotypes of G. parviflora and one of G. salicifolia have been tentatively identified. Using micro-titre plate broth dilution assays, antibacterial and antifungal activity of all chemotypes was investigated. In this regard, the 'green oil' chemotype, restricted to G. parviflora, with major components linalool, geijerene/pregeijerene, 1,8-cineol and bicyclogermacrene, demonstrated the highest antimicrobial and free radical scavenging activity. Thus, in the light of traditional use reports of local analgaesia and bioactivity demonstrated in the current study, oils from select chemotypes of G. parviflora may be useful in suitably compounded lotions and creams designed for topical antimicrobial applications and local pain relief. In addition, because major components are known for insecticidal activities, such lotions may also be useful as topically applied insect repellents.