Pharmacological and behavioral investigation of putative self-medicative plants in Budongo chimpanzee diets.

Wild chimpanzees consume a variety of plants to meet their dietary needs and maintain wellbeing. While some plants have obvious value, others are nutritionally poor and/or contain bioactive toxins which make ingestion costly. In some cases, these nutrient-poor resources are speculated to be medicinal, thought to help individuals combat illness. In this study, we observed two habituated chimpanzee communities living in the Budongo Forest, Uganda, and collected 17 botanical samples associated with putative self-medication behaviors (e.g., bark feeding, dead wood eating, and pith-stripping) or events (e.g., when consumer had elevated parasite load, abnormal urinalysis, or injury). In total, we selected plant parts from 13 species (nine trees and four herbaceous plants). Three extracts of different polarities were produced from each sample using n-hexane, ethyl acetate, and methanol/water (9/1, v/v) and introduced to antibacterial and anti-inflammatory in vitro models. Extracts were evaluated for growth inhibition against a panel of multidrug-resistant clinical isolates of bacteria, including ESKAPE strains and cyclooxygenase-2 (COX-2) inhibition activity. Pharmacological results suggest that Budongo chimpanzees consume several species with potent medicinal properties. In the antibacterial library screen, 45 out of 53 extracts (88%) exhibited ≥40% inhibition at a concentration of 256 µg/mL. Of these active extracts, 41 (91%) showed activity at ≤256µg/mL in subsequent dose-response antibacterial experiments. The strongest antibacterial activity was achieved by the n-hexane extract of Alstonia boonei dead wood against Staphylococcus aureus (IC50: 16 µg/mL; MIC: 32 µg/mL) and Enterococcus faecium (IC50: 16 µg/mL; MIC: >256 µg/mL) and by the methanol-water extract of Khaya anthotheca bark and resin against E. faecium (IC50: 16 µg/mL; MIC: 32 µg/mL) and pathogenic Escherichia coli (IC50: 16 µg/mL; MIC: 256 µg/mL). We observed ingestion of both these species by highly parasitized individuals. K. anthotheca bark and resin were also targeted by individuals with indicators of infection and injuries. All plant species negatively affected growth of E. coli. In the anti-inflammatory COX-2 inhibition library screen, 17 out of 51 tested extracts (33%) showed ≥50% COX-2 inhibition at a concentration of 5 µg/mL. Several extracts also exhibited anti-inflammatory effects in COX-2 dose-response experiments. The K. anthotheca bark and resin methanol-water extract showed the most potent effects (IC50: 0.55 µg/mL), followed by the fern Christella parasitica methanol-water extract (IC50: 0.81 µg/mL). This fern species was consumed by an injured individual, a feeding behavior documented only once before in this population. These results, integrated with associated observations from eight months of behavioral data, provide further evidence for the presence of self-medicative resources in wild chimpanzee diets. This study addresses the challenge of distinguishing preventative medicinal food consumption from therapeutic self-medication by integrating pharmacological, observational, and health monitoring data-an essential interdisciplinary approach for advancing the field of zoopharmacognosy.

Malnutrition Is Highly Prevalent in Patients With Chronic Pancreatitis and Characterized by Loss of Skeletal Muscle Mass but Absence of Impaired Physical Function.

Background/Aims: Patients with chronic pancreatitis (CP) have an increased risk of malnutrition, a condition linked to reduced muscle mass and physical performance. We have investigated the risk factors, phenotypic presentation, and health implications associated with malnutrition in CP. Materials and Methods: In a multicenter cross-sectional study we recruited patients with confirmed CP and healthy volunteers as a control group. Malnutrition was diagnosed according to the criteria proposed by the Global Leadership Initiative on Malnutrition. We performed detailed examinations of body composition and physical function as well as testing of routine blood parameters and markers of inflammation. Results: We included 66 patients [mean (±SD) age: 56.0 (±14.5) years; 51 males] and an equal number of age- and sex-matched controls. Moderate malnutrition was diagnosed in 21% (n = 14) and severe malnutrition in 42% (n = 28) of patients. Besides weight loss malnourished patients showed lower fat and skeletal muscle mass compared to both non-malnourished subjects and healthy controls. Only in severe malnutrition, blood parameters reflected elevated inflammation and reduced muscle reserves. Handgrip strength in patients did not differ by nutritional status but there was a significant correlation (rho = 0.705, p < 0.001) with skeletal muscle mass. Although 20 patients (30%) had pathologically reduced skeletal muscle mass, only two individuals (3%) had sarcopenia with concomitantly reduced handgrip strength. Conclusion: Malnutrition is a frequent complication of CP characterized by loss of skeletal muscle mass. As this condition becomes evident only at an advanced stage, regular testing for altered body composition is recommended. Suitable biomarkers and the link between loss of muscle mass and physical function require further investigation. Clinical Trial Registration: [https://clinicaltrials.gov/ct2/show/NCT04474743], identifier [NCT04474743].

Molecular Mechanism Contributing to Malnutrition and Sarcopenia in Patients with Liver Cirrhosis.

Liver cirrhosis is frequently accompanied by disease-related malnutrition (DRM) and sarcopenia, defined as loss of skeletal muscle mass and function. DRM and sarcopenia often coexist in cirrhotic patients and are associated with increased morbidity and mortality. The clinical manifestation of both comorbidities are triggered by multifactorial mechanisms including reduced nutrient and energy intake caused by dietary restrictions, anorexia, neuroendocrine deregulation, olfactory and gustatory deficits. Maldigestion and malabsorption due to small intestinal bacterial overgrowth, pancreatic insufficiency or cholestasis may also contribute to DRM and sarcopenia. Decreased protein synthesis and increased protein degradation is the cornerstone mechanism to muscle loss, among others mediated by disease- and inflammation-mediated metabolic changes, hyperammonemia, increased myostatin and reduced human growth hormone. The concise pathophysiological mechanisms and interactions of DRM and sarcopenia in liver cirrhosis are not completely understood. Furthermore, most knowledge in this field are based on experimental models, but only few data in humans exist. This review summarizes known and proposed molecular mechanisms contributing to malnutrition and sarcopenia in liver cirrhosis and highlights remaining knowledge gaps. Since, in the prevention and treatment of DRM and sarcopenia in cirrhotic patients, more research is needed to identify potential biomarkers for diagnosis and development of targeted therapeutic strategies.

An epoxide hydrolase involved in the biosynthesis of an insect sex attractant and its use to localize the production site.

Epoxide hydrolases (EHs) are enzymes occurring in virtually any living organism. They catalyze the hydrolysis of epoxide containing lipids and are involved in crucial mechanisms, such as the detoxification of xenobiotics or the regulation of inflammation and blood pressure. Here, we describe a function of a putative EH gene in the biosynthesis of a sex attractant in the jewel wasp Nasonia vitripennis and use this gene to localize the site of pheromone production. Males of this parasitic wasp release a mixture of (4R,5R)-( threo-) and (4R,5S)-( erythro-)5-hydroxy-4-decanolide (HDL) to attract virgin females. Using a stable isotope labeled precursor, we demonstrated that vernolic acid ( erythro-12,13-epoxy-octadec-9Z-enoic acid) is converted by N. vitripennis males to threo-HDL. This suggested the involvement of an EH in hydrolyzing the fatty acid epoxide under inversion of the stereochemistry into the respective diol, which might be further processed by chain shortening and lactonization to HDL. We cloned a putative N. vitripennis EH gene (Nasvi-EH1) encoding 470 amino acids and localized its transcripts in the male rectal papillae by in situ RT-PCR. Chemical analyses and histological studies confirmed that males synthesize the sex attractant in the rectal vesicle and release it via the anal orifice. Involvement of Nasvi-EH1 in HDL biosynthesis was established by RNAi-mediated gene silencing. Injection of Nasvi-EH1 dsRNA into male abdomens inhibited pheromone biosynthesis by 55% and suppressed the targeted gene transcripts in the rectal vesicle by 95%.

A male sex pheromone in a parasitic wasp and control of the behavioral response by the female's mating status.

Male insects may increase their chance of successful reproduction by releasing pheromones that attract females or elicit sexual acceptance. In parasitic wasps, male pheromones have been suggested for a few species but no chemicals have been identified so far. Here we report the first identification of a male sex pheromone in parasitic Hymenoptera. In abdomens of male jewel wasps, Nasonia vitripennis Walker, we found a mixture of (4R,5R)- and (4R,5S)-5-hydroxy-4-decanolide (HDL), which was released intermittently and attracted virgin females, but no males, in an olfactometer bioassay. However, only a few minutes after copulation mated females avoided the male-derived pheromone. Neither preference nor avoidance was shown by mated females after 24 h and even after they had been allowed to oviposit for 6 days. Nasonia vitripennis females normally mate only once. Thus, their variable response to the sex attractant depending on the mating status makes sense from an evolutionary perspective. Firstly, it increases the chance of virgins to be inseminated. Secondly, by terminating the response or even avoiding the male pheromone, mated females decrease the probability of encountering males and being disturbed by their courtship activities when searching for new oviposition sites.

Enzymatic Baeyer-Villiger oxidation as the key step in decano-4-lactone and decano-5-lactone degradation by Sporobolomyces odorus.

The biosyntheses of aroma active gamma- and delta-lactones have been previously characterized in yeasts and plants by incubation of labeled fatty acid derivatives. The lactones were considered as end products. Liquid cultures of the lactone-producing yeast Sporobolomyces odorus were used to investigate catabolic pathways of the lactones by incubation of ethyl (+/-)-5-hydroxy(1-(13)C1)decanoate ((13C)-1b) and methyl (+/-)-4-hydroxy(1-(13)C1)decanoate ((13C)-7a). Aliquots of the culture broth were analyzed with GC/MS after CH2N2 derivatization. S. odorus degraded (13C)-1b to 5-oxo(1-(13)C1)decanoic acid ((13C)-2c) and, subsequently, to pentyl (1-(13)C1)pentanedioate ((13C)-3c) and 3-[(1-(13)C1)carboxypropyl] hexanoate ((13C)-4c) by a Baeyer-Villiger-type oxidation (BVO). In addition, the oxidation of (13C)-7a to 4-oxo(1-(13)C1)decanoic acid ((13C)-8c) and a BVO of (13C)-8c to hexyl (1-(13)C1)butanedioate ((13C)-9c) is reported. So far, BVO has been observed in bacteria and some fungi; the data presented indicate a BVO catalyzed by the yeast S. odorus in the course of endogenous lactone metabolism.