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Pigeon pea (Cajanus cajan (L.) Millsp.) is a traditional Chinese medicinal plant widely utilized in folk medicine due to its significant pharmacological and nutritional properties. Cajaninstilbene acid (CSA), a stilbene compound derived from pigeon pea leaves, has been extensively investigated since the 1980s. A thorough understanding of CSA’s mechanisms of action and its therapeutic effects on various diseases is crucial for developing novel therapeutic approaches. This paper presents an overview of recent research advancements concerning the biological activities and mechanisms of CSA and its derivatives up to February 2024. The review encompasses discussions on the in vivo metabolism of CSA and its derivatives, including antipathogenic micro-organisms activity, anti-tumor activity, systematic and organ protection activity (such as bone protection, cardiovascular protection, neuroprotection), anti-inflammatory activity, antioxidant activity, immune regulation as well as action mechanism of CSA and its derivatives. The most studied activities are antipathogenic micro-organisms activities. Additionally, the structure–activity relationships of CSA and its derivatives as well as the total synthesis of CSA are explored, highlighting the potential for developing new pharmaceutical agents. This review aims to provide a foundation for future clinical applications of CSA and its derivatives.

Three previously unidentified dihydrostilbene glycosides, named oleiferaside A (1), oleiferaside B (2), and oleiferaside C (3), were discovered through a phytochemical exploration on Camellia oleifera Abel. leaves. Additionally, nine known secondary metabolites (4–12) were also identified. The undescribed secondary metabolites 1–3 were elucidated as 3,5-dimethoxydihydrostilbene 4′-O-α-l-arabinofuranosyl-(1 → 6)-β-d- glucopyranoside, 3,5-dimethoxydihydrostilbene 4′-O-α-l-arabinopyranosyl-(1 → 6)-β-d- glucopyranoside and 3,5-dimethoxydihydrostilbene 4′-O-β-d-apiofuranosyl-(1 → 6)-β-d- glucopyranoside, respectively. HR-MS and NMR spectroscopy were utilized for determining the structures of the isolates. The natural products were assessed for their anti-inflammatory effect using RAW264.7 macrophage stimulated by LPS. The findings demonstrated that compounds 1–4 exhibited inhibitory activities on NO and PGE2 production without causing cytotoxicity. These observations suggest that these compounds may have potential anti-inflammatory properties.

Abstract Background Traditional herbs played a crucial role in the health care of the Hakka people. However, studies to identify these traditional herbs are few. Here we document and assess the potential of these plants for treating microbial infections. Many herbs used by the Hakka people could potentially be a novel medicinal resource. Methods Local herb markets were surveyed via semi-structured interviews, complemented by direct observations to obtain information on herbal usage. For each herb selected for this study, extracts in four different solvents were prepared, and tested for activity against 20 microorganisms, as well as cancerous and noncancerous cells. All data were subjected to cluster analysis to discover relationships among herbs, plant types, administration forms, solvents, microorganisms, cells, etc., with the aim to discern promising herbs for medicine. Results Ninety-seven Hakka herbs in Ganzhou were documented from 93 plants in 62 families; most are used for bathing (97%), or as food, such as tea (32%), soup (12%), etc. Compared with the Chinese Pharmacopoeia and Chinese Materia Medica, 24 Hakka medicines use different plant parts, and 5 plants are recorded here for the first time as traditional medicines. The plant parts used were closely related with the life cycle: annual and perennial herbs were normally used as a whole plant, and woody plants as (tender) stem and leaf, indicating a trend to use the parts that are easily collected. Encouragingly, 311 extracts (94%) were active against one or more microorganisms. Most herbs were active against Gram-positive bacteria, such as Staphylococcus aureus (67%), Listeria innocua (64%), etc. Cytotoxicity was often observed against a tumor cell, but rarely against normal cells. Considering both antimicrobial activity and cytotoxicity, many herbs reported in this study show promise as medicine. Conclusion Hakka people commonly use easily-collected plant parts (aerial parts or entire herb) as medicine. External use of decoctions dominated, and may help combating microbial infections. The results offer promising perspectives for further research since little phytopharmacology and phytochemistry has been published to date. Graphical Abstract

Chimonanthus grammatus is used as Hakka traditional herb to treat cold, flu, etc. So far, the phytochemistry and antimicrobial compounds have not been well investigated. In this study, the orbitrap-ion trap MS was used to characterize its metabolites, combined with a computer-assisted structure elucidation method, and the antimicrobial activities were assessed by a broth dilution method against 21 human pathogens, as well as the bioassay-guided purification work to clarify its main antimicrobial compounds. A total of 83 compounds were identified with their fragmentation patterns, including terpenoids, coumarins, flavonoids, organic acids, alkaloids, and others. The plant extracts can strongly inhibit the growth of three Gram-positive and four Gram-negative bacteria, and nine active compounds were bioassay-guided isolated, including homalomenol C, jasmonic acid, isofraxidin, quercitrin, stigmasta-7,22-diene-3β,5α,6α-triol, quercetin, 4-hydroxy-1,10-secocadin-5-ene-1,10-dione, kaempferol, and E-4-(4,8-dimethylnona-3,7-dienyl)furan-2(5H)-one. Among them, isofraxidin, kaempferol, and quercitrin showed significant activity against planktonic Staphylococcus aureus (IC50 = 13.51, 18.08 and 15.86 µg/ml). Moreover, their antibiofilm activities of S. aureus (BIC50 = 15.43, 17.31, 18.86 µg/ml; BEC50 = 45.86, ≥62.50, and 57.62 µg/ml) are higher than ciprofloxacin. The results demonstrated that the isolated antimicrobial compounds played the key role of this herb in combating microbes and provided benefits for its development and quality control, and the computer-assisted structure elucidation method was a powerful tool for chemical analysis, especially for distinguishing isomers with similar structures, which can be used for other complex samples.

The presence of sugar in the gut causes induction of SGLT1, the sodium/glucose cotransporter in intestinal epithelial cells (enterocytes), and this is accompanied by stimulation of sugar absorption. Sugar sensing was suggested to involve a G-protein coupled receptor and cAMP - protein kinase A signalling, but the sugar receptor has remained unknown. We show strong expression and co-localization with SGLT1 of the β2-adrenergic receptor (β2-AR) at the enterocyte apical membrane and reveal its role in stimulating glucose uptake from the gut by the sodium/glucose-linked transporter, SGLT1. Upon heterologous expression in different reporter systems, the β2-AR responds to multiple sugars in the mM range, consistent with estimated gut sugar levels after a meal. Most adrenergic receptor antagonists inhibit sugar signaling, while some differentially inhibit epinephrine and sugar responses. However, sugars did not inhibit binding of I125-cyanopindolol, a β2-AR antagonist, to the ligand-binding site in cell-free membrane preparations. This suggests different but interdependent binding sites. Glucose uptake into everted sacs from rat intestine was stimulated by epinephrine and sugars in a β2-AR-dependent manner. STD-NMR confirmed direct physical binding of glucose to the β2-AR. Oral administration of glucose with a non-bioavailable β2-AR antagonist lowered the subsequent increase in blood glucose levels, confirming a role for enterocyte apical β2-ARs in stimulating gut glucose uptake, and suggesting enterocyte β2-AR as novel drug target in diabetic and obese patients. Future work will have to reveal how glucose sensing by enterocytes and neuroendocrine cells is connected, and whether β2-ARs mediate glucose sensing also in other tissues.

Abstract Background Hepatic metastasis is the primary and direct cause of death in individuals with colorectal cancer (CRC) attribute to lack of effective therapeutic targets. The present study aimed to identify potential druggable candidate targets for patients with liver metastatic CRC. Methods The transcriptional profiles of super‐enhancers (SEs) in primary and liver metastatic CRC were evaluated in publicly accessible CRC datasets. Immunohistochemistry of human CRC tissues was conducted to determine the expression level of CDK12. Cellular proliferation, survival and stemness were examined upon CDK12 inhibition by shCDK12 or a selective CDK12 inhibitor named SR‐4835 with multiple in vitro and in vivo assays. RNA sequencing and bioinformatics analyses were carried out to investigate the mechanisms of CDK12 inhibition in CRC cells. Results We identified CDK12 as a driver gene for direct hepatic metastasis in CRC. Suppression of CDK12 led to robust inhibition of proliferation, survival and stemness. Mechanistically, CDK12 intervention preferentially repressed the transcription of SE‐associated genes. Integration of the SE landscape and RNA sequencing, BCL2L1 and CCDC137 were identified as SE‐associated oncogenic genes to strengthen the abilities of cellular survival, proliferation and stemness, eventually increasing liver metastasis of CRC. Conclusions Our data highlight the potential of CDK12 and SE‐associated oncogenic transcripts as therapeutic targets for patients with liver metastatic CRC.

The newly emerged SARS-CoV-2 strains from the coronavirus (CoV) family is causing one of the most disruptive pandemics of the past century. Developing antiviral drugs is a challenge for the scientific community and pharmaceutical industry. Given the health emergency, repurposing of existing antiviral, antiinflammatory or antimalarial drugs is an attractive option for controlling SARS-CoV-2 with drugs. However, phytochemicals selected based on ethnomedicinal information as well as in vitro antiviral studies could be promising as well. Here, we summarise the phytochemicals with reported anti-CoV activity, and further analyzed them computationally to accelerate validation for drug development against SARS-CoV-2. This systematic review started from the most potent phytocompounds (IC50 in μM) against SARS-CoV, followed by a cluster analysis to locate the most suitable lead(s). The advanced molecular docking used the crystallography structure of SARS-CoV-2-cysteine-like protease (SARS-CoV-2-3CLpro) as a target. In total, seventy-eight phytochemicals with anti-CoV activity against different strains in cellular assays, were selected for this computational study, and compared with two existing repurposed FDA-approved drugs: lopinavir and ritonavir. This review brings insights in the potential application of phytochemicals and their derivatives, which could guide researchers to develop safe drugs against SARS-CoV-2.

Tetradenia riparia Hochsteter codd. (Lamiaceae) in its native African continent, is considered one of the most popular aromatic medicinal plants. In folk medicine it may be used as an infusion to treat respiratory problems, cough, headache, stomach pain, diarrhea, fever, malaria, and dengue; and in the form of compresses it is applied for the relief of headaches and toothaches. The species T. riparia has been researched for decades to isolate and identify chemical constituents present in extracts or essential oil obtained from the leaves, floral buds, or stems of this plant. The present study reviews the scientific literature on ethnomedicinal, phytochemical, and pharmacological aspects of T. riparia. We discuss issues related to the botanical and geographical description of the species, ethnobotanical uses, phytochemical studies on its essential oil and extracts, and biological activities of T. riparia. Several compounds have already been isolated from leaves, such as ibozol, 7α-hydroxyroileanone, 1′,2′-dideacetylboronolide, 8(14),15-sandaracopimaradiene-7α,18-diol; 5,6-dihydro-α-pyrone and α-pyrone. Terpenes predominated in the essential oil, comprising monoterpenes, sesquiterpenes, diterpenes, hydrocarbons, and oxygenates. Most phytocompounds were isolated from the leaves and flower buds, namely fenchone, 14-hydroxy-9-epi (E)-caryophyllene, 9β, 13β-epoxy-7-abietene, and 6,7-dehydroroileanone. These compounds provide the species a high pharmacological potential, with antimicrobial, antioxidant, antitumor, analgesic, anti-leishmania, anti-tuberculosis, and anti-parasitic activities. Therefore, this species is a promising herbal medicine.

The stem of Picrasma quassioides (PQ) was recorded as a prominent traditional Chinese medicine, Kumu, which was effective for microbial infection, inflammation, fever, and dysentery, etc. At present, Kumu is widely used in China to develop different medicines, even as injection (Kumu zhusheye), for combating infections. However, the chemical basis of its antimicrobial activity has still not been elucidated. To examine the active chemicals, its stem was extracted to perform bioassay-guided purification against Staphylococcus aureus and Escherichia coli. In this study, two types of columns (normal and reverse-phase) were used for speedy bioassay-guided isolation from Kumu, and the active peaks were collected and identified via an UHPLC-Orbitrap-Ion Trap Mass Spectrometer, combined with MS Fragmenter and ChromGenius. For identification, the COCONUT Database (largest database of natural products) and a manually built PQ database were used, in combination with prediction and calculation of mass fragmentation and retention time to better infer their structures, especially for isomers. Moreover, three standards were analyzed under different conditions for developing and validating the MS method. A total of 25 active compounds were identified, including 24 alkaloids and 1 triterpenoid against S. aureus, whereas only β-carboline-1-carboxylic acid and picrasidine S were active against E. coli. Here, the good antimicrobial activity of 18 chemicals was reported for the first time. Furthermore, the spectrum of three abundant β-carbolines was assessed via their IC50 and MBC against various human pathogens. All of them exhibited strong antimicrobial activities with good potential to be developed as antibiotics. This study clearly showed the antimicrobial chemical basis of Kumu, and the results demonstrated that HRMS coupled with MS Fragmenter and ChromGenius was a powerful tool for compound analysis, which can be used for other complex samples. Beta-carbolines reported here are important lead compounds in antibiotic discovery.

Helminths, with an estimated 1.5 billion annual global infections, are one of the major health challenges worldwide. The current strategy of the World Health Organization to prevent helminth infection includes increasing hygienic awareness, providing better sanitation and preventative anthelmintic drug therapy in vulnerable populations. Nowadays, anthelmintic drugs are used heavily in livestock, both in case of infection and as a preventative measure. However, this has led to the development of resistance against several of the most common drugs, such as levamisole, ivermectin and thiabendazole. As many as 70% of the livestock in developed countries now has helminths that are drug resistant, and multiple resistance is common. Because of this, novel anthelmintics are urgently needed to help combat large-scale production losses. Prior to this review, no comprehensive review of the anthelmintic effects of essential oils and their components existed. Multiple review articles have been published on the uses of a single plant and its extracts that only briefly touch upon their anthelmintic activity. This review aims to provide a detailed overview of essential oils and their components as anthelmintic treatment against a wider variety of helminths.

This study evaluated the effect of the extract and fractions of Bauhinia holophylla on Candida albicans planktonic growth, biofilm formation, mature biofilm, and hyphae growth. Three C. albicans strains (SC5314, ATCC 18804, and ATCC 10231) were tested. The crude extract and the fractions were obtained by exhaustive percolation and liquid–liquid partition, respectively. Phytochemical analyses of B. holophylla extract and fractions were performed using high-performance liquid chromatography coupled with a diode-array detector and mass spectrometry (HPLC-DAD-MS). A microdilution assay was used to evaluate the effect of the B. holophylla extract and fractions on C. albicans planktonic growth, and crystal violet staining was used to measure the total biomass of the biofilm. Hyphae growth was analyzed using light microscopy. Thirteen flavonoids were identified, with a predominance of the flavonol-3-O-glycoside type based on quercetin, myricetin, and kaempferol. Flavonoid-rich fractions of B. holophylla leaves displayed antifungal activity and inhibited both biofilm formation and hyphae growth in all the tested strains, but were not effective on C. albicans planktonic growth and mature biofilm. This study indicates that flavonoid-rich fractions from B. holophylla leaves interfere with the virulence of Candida species and support the use of Bauhinia spp. in folk medicine to treat infections.

To uncover potential anti-aging capacities of Traditional Chinese Medicine (TCM), the nematode Caenorhabditis elegans was used to investigate the effects of Eucommia ulmoides and Cuscuta chinensis extracts, selected by screening seven TCM extracts, on different healthspan parameters. Nematodes exposed to E. ulmoides and C. chinensis extracts, starting at the young adult stage, exhibited prolonged lifespan and increased survival after heat stress as well as upon exposure to the pathogenic bacterium Photorhabdus luminescens, whereby the survival benefits were monitored after stress initiation at different adult stages. However, only C. chinensis had the ability to enhance physical fitness: the swimming behavior and the pharyngeal pumping rate of C. elegans were improved at day 7 and especially at day 12 of adulthood. Finally, monitoring the red fluorescence of aged worms revealed that only C. chinensis extracts caused suppression of intestinal autofluorescence, a known marker of aging. The results underline the different modes of action of the tested plants extracts. E. ulmoides improved specifically the physiological fitness by increasing the survival probability of C. elegans after stress, while C. chinensis seems to be an overall healthspan enhancer, reflected in the suppressed autofluorescence, with beneficial effects on physical as well as physiological fitness. The C. chinensis effects may be hormetic: this is supported by increased gene expression of hsp-16.1 and by trend, also of hsp-12.6.

A biologically guided isolation of secondary metabolites from Cousinia alata Schrenk wild plant growing in Akmola region, Kazakhstan, led to the isolation of the bioactive diterpene grindelic acid (1). Six flavonoids were also isolated and identified as retusine (2), pachipodol (3), jaranol (4), penduletin (5), casticin (6), and 5, 7, 3′-trihydroxy-3, 4′-dimethoxyflavone (7). Penduletin (5) showed moderate cytotoxic activity assay. Grindelic acid exhibited promising cytotoxic activity against the Artemia salina nauplii and antibacterial activity against Staphylococcus aureus, Bacillus cereus, and Salmonella enteritidis. The presence of the essential pharmacophoric features of histone deacetylase (HDAC) inhibitors in the structure of grindelic acid encouraged us to run a molecular docking study against the HDAC enzyme to understand its mechanism of action on a molecular level. Grindelic acid showed a binding mode of interaction similar to that of the cocrystallized ligand and exhibited good binding affinity against HDAC with the binding free energy of −18.70 kcal/mol. The structures of isolated compounds were determined by MS, 1D, and 2D NMR spectroscopy methods. Compounds (1–7) were isolated for the first time from Cousinia genus.

Approximately 270 species of mushrooms have been reported as potentially useful for human health. However, few mushrooms have been studied for bioactive compounds that can be helpful in treating various diseases. Like other natural regimens, the mushroom treatment appears safe, as could be expected from their long culinary and medicinal use. This review aims to provide a critical discussion on clinical trial evidence for mushrooms to treat patients with diverse types of cancer. In addition, the review also highlights the identified bioactive compounds and corresponding mechanisms of action among the explored mushrooms. Furthermore, it also discusses mushrooms with anticancer properties, demonstrated either in vitro and/or in vivo models, which have never been tested in clinical studies. Several mushrooms have been tested in phase I or II clinical trials, mostly for treating breast cancer (18.6%), followed by colorectal (14%) and prostate cancer (11.6%). The majority of clinical studies were carried out with just 3 species: Lentinula edodes (22.2%), Coriolus versicolor, and Ganoderma lucidum (both 13.9%); followed by two other species: Agaricus bisporus and Grifola frondosa (both 11.1%). Most in vitro cell studies use breast cancer cell lines (43.9%), followed by lung (14%) and colorectal cancer cell lines (13.1%), while most in vivo animal studies are performed in mice tumor models (58.7%). Although 32 species of mushrooms at least show some promise for the treatment of cancer, only 11 species have been tested clinically thus far. Moreover, most clinical studies have investigated fewer numbers of patients, and have been limited to phase III or IV. Therefore, despite the promising preclinical and clinical data publication, more solid scientific efforts are required to clarify the therapeutic value of mushrooms in oncology.

Different parts of Cnestis ferruginea are used in traditional African medicine for treating infectious diseases such as dysentery, bronchitis, eye troubles, conjunctivitis, sinusitis, gonorrhea, and syphilis. Despite its long traditional use in the treatment of infections, this plant is not well studied for its in vitro antimicrobial properties. Therefore, the present study aims to establish the antimicrobial activity profile of extracts from this plant, as well as to isolate and evaluate the antimicrobial activity of the most abundant bioactive compound in C. ferruginea leaves through bioassay-guided purification, using Staphylococcus aureus as a target organism. Although both methanol and water extracts of the plant leaves proved active against S. aureus, a water extract was pursued, and subjected further to liquid-liquid partitioning (ethyl acetate, butanol, and water). The ethyl acetate fraction was found to be the most potent and was subjected to silica gel chromatography. In total, 250 fractions were obtained, and those with similar TLC profiles were clustered into 22 major groups, of which pooled fraction-F6 (83 mg) was the most potent. Additional purification by HPLC resulted in two active peaks, which were identified, using a combination of NMR and mass spectrometry, as hydroquinone and caffeic acid methyl ester. Their antimicrobial activity was confirmed using a microdilution protocol on S. aureus, where hydroquinone had a stronger activity (MIC50 = 63 μg/mL) compared to caffeic acid methyl ester (>200 μg/mL). Traditionally this plant is used as an aqueous preparation to treat many infections, and the present study also demonstrated antimicrobial activity in the aqueous extract, which appears due mainly to two major water-soluble compounds isolated through bioassay-guided purification. This supports the clinical use of the aqueous extract of C. ferruginea leaves as a phytotherapeutic for bacterial infections.

Holarrhena pubescens is an important medicinal plant of the Apocynaceae family that is widely distributed over the Indian subcontinent. The plant is extensively used in Ayurveda and other traditional medicinal systems without obvious adverse effects. Beside notable progress in the biological and phytochemical evaluation of this plant over the past few years, comprehensive reviews of H. pubescens are limited in scope. It has economic importance due to the extensive use of seeds as an antidiabetic. Furthermore, the plant is extensively reported in traditional uses among the natives of Asia and Africa, while scientifical validation for various ailments has not been studied either in vitro or in vivo. This review aims to summarize information on the pharmacology, traditional uses, active constituents, safety and toxicity of H. pubescens. Chemical analysis of H. pubescens extracts revealed the presence of several bioactive compounds, such as conessine, isoconnessine, conessimine, conimine, conessidine, conkurchicine, holarrhimine, conarrhimine, mokluangin A-D and antidysentericine. Overall, this review covers the ethnopharmacology, phytochemical composition, and pharmacological potential of H. pubescens, with a critical discussion of its toxicity, biological activities (in vitro and in vivo), the mechanism of action, as well as suggestions for further basic and clinical research.

Holigarna caustica (Dennst.) Oken is used by the tribes of Northeast India for the treatment of intestinal problems. Therefore, the present study was undertaken to investigate the active principles of this plant responsible for its anthelmintic activity, using bioassay-guided fractionation. An ethanol extract of H. caustica fruit was fractionated on a silica gel column, followed by HPLC, while nematicidal activity was followed throughout on Caenorhabditis (C.) elegans as a model organism. Our study constitutes the first nematicidal report for this plant. Bioassay-guided purification led to the isolation of one compound (IC50 = 0.4 µM) as the only active constituent in the most active fraction. The compound was identified as linoleic acid based on spectroscopic data (1H and 13C NMR and ESI-MS). No cytotoxicity was observed in the crude extract or in linoleic acid (up to 356 µM). The results support the use of H. caustica for the treatment of intestinal problems by traditional healers in India.

Chikungunya and yellow fever virus cause vector-borne viral diseases in humans. There is currently no specific antiviral drug for either of these diseases. Banana plants are used in traditional medicine for treating viral diseases such as measles and chickenpox. Therefore, we tested selected banana cultivars for their antiviral but also cytotoxic properties. Different parts such as leaf, pseudostem and corm, collected separately and extracted with four different solvents (hexane, acetone, ethanol, and water), were tested for in vitro antiviral activity against Chikungunya virus (CHIKV), enterovirus 71 (EV71), and yellow fever virus (YFV). Extracts prepared with acetone and ethanol from leaf parts of several cultivars exhibited strong (EC50 around 10 μg/mL) anti-CHIKV activity. Interestingly, none of the banana plant extracts (concentration 1–100 µg/mL) were active against EV71. Activity against YFV was restricted to two cultivars: Namwa Khom–Pseudostem–Ethanol (5.9 ± 5.4), Namwa Khom–Corm–Ethanol (0.79 ± 0.1) and Fougamou–Corm–Acetone (2.5 ± 1.5). In most cases, the cytotoxic activity of the extracts was generally 5- to 10-fold lower than the antiviral activity, suggesting a reasonable therapeutic window.

Ten banana (Musa spp.) cultivars were studied for their antimicrobial properties. Three plant parts (corm, pseudostem and leaves) were collected separately and extracted with different solvents, viz., hexane, acetone, ethanol and water. The 50% inhibitory concentration (IC50) was evaluated using a broth microdilution assay. Eight human bacterial and one fungal pathogen were tested. Acetone and ethanol extract(s) often exhibited significant antimicrobial activity, while hexane extracts were less active. Aqueous extracts often showed microbial growth, possibly by endophytes. Leaf extracts were most active, followed by pseudostem, and corm was least active. All the tested banana cultivars were found to contain antimicrobials, as demonstrated by inhibition of selected human pathogens. However, cultivars such as Dole, Saba, Fougamou, Namwah Khom, Pelipita and Mbwazirume showed a broad-spectrum activity, inhibiting all tested pathogens. Other cultivars such as Petit Naine and Kluai Tiparot showed a narrow-spectrum activity, including antibiofilm activity against Candida albicans. Our results support the use of different parts of banana plants in traditional human medicine for infections, including diarrhea and dysentery, and some sexually transmitted diseases, as well as for packaging spoilable materials like food.

Intestinal parasitic nematodes infect approximately two billion people worldwide. In the absence of vaccines for human intestinal nematodes, control of infections currently relies mainly on chemotherapy, but resistance is an increasing problem. Thus, there is an urgent need for the discovery and development of new anthelmintic drugs, especially ones with novel mechanisms of action. Medicinal plants hold great promise as a source of effective treatments, including anthelmintic therapy. They have been used traditionally for centuries and are mostly safe (if not, their toxicity is well-known). However, in most medicinal plants the compounds active against nematodes have not been identified thus far. The free-living nematode C. elegans was demonstrated to be an excellent model system for the discovery of new anthelmintics and for characterizing their mechanism of action or resistance. The compounds discussed in this review are of botanical origin and were published since 2002. Most of them need further studies of their toxicity, mechanisms and structure-activity relationship to assess more fully their potential as drugs.

Salvia officinalis is frequently used in traditional Algerian medicine to treat diverse microbial infections, including oral and vaginal candidiasis. The aerial parts of S. officinalis collected in Annaba, Algeria were extracted in parallel by maceration with four solvents viz. hexane, acetone, methanol and water. All the extracts were tested in vitro against several Candida species: C. albicans, C. glabrata, and C. parapsilosis. Furthermore, the activity against biofilm-forming C. albicans was investigated using bioassay-guided fractionation. A large-scale extract was prepared via maceration in methanol, followed by fractionation on a silica gel column using increasingly polar mixtures of n-hexane, ethyl acetate, methanol, and acetic acid as mobile phase, to yield a total of 150 fractions. Two major active fractions (F-31 and F-39), were further separated by HPLC, resulting in several active chromatographic peaks. Carnosol and 12-methoxy-trans-carnosic acid were isolated as two major active compounds, and identified by a combination of NMR and mass spectrometry. The biofilm inhibitory concentration showed that 12-methoxy-trans-carnosic acid is more effective than carnosol with BIC50 values of 94 μM (95% confidence interval, 78.9–112.1 μM) and 314 μM (95% confidence interval, 200.7–491.2 μM), respectively. The present study supports the traditional use of sage in the treatment of various fungal infections caused by Candida. Further studies of the bioactive compounds in an in vivo Candida biofilm model are required to validate their clinical potential as antifungals.

Vancomycin is a glycopeptide antibiotic that inhibits transpeptidation during cell wall synthesis by binding to the D-Ala-D-Ala termini of lipid II. For long, it has been used as a last resort antibiotic. However, since the emergence of the first vancomycin-resistant enterococci in 1987, vancomycin resistance has become widespread, especially in hospitals. We have synthesized and evaluated 110 vancomycin analogs modified at the C-terminal carboxyl group of the heptapeptide moiety with R2NHR1NH2 substituents. Through iterative optimizations of the substituents, we identified vancomycin analogs that fully restore (or even exceed) the original inhibitory activity against vancomycin-resistant enterococci (VRE), vancomycin-intermediate (VISA) and vancomycin-resistant Staphylococcus aureus (VRSA) strains. The best analogs have improved growth inhibitory activity and in vitro therapeutic indices against a broad set of VRE and methicillin-resistant S. aureus (MRSA) isolates. They also exceed the activity of vancomycin against Clostridium difficile ribotypes. Vanc-39 and Vanc-42 have a low probability to provoke antibiotic resistance, and overcome different vancomycin resistance mechanisms (VanA, VanB, and VanC1).

In the present study, we tested in vitro different parts of 35 plants used by tribals of the Similipal Biosphere Reserve (SBR, Mayurbhanj district, India) for the management of infections. From each plant, three extracts were prepared with different solvents (water, ethanol, and acetone) and tested for antimicrobial (E. coli, S. aureus, C. albicans); anthelmintic (C. elegans); and antiviral (enterovirus 71) bioactivity. In total, 35 plant species belonging to 21 families were recorded from tribes of the SBR and periphery. Of the 35 plants, eight plants (23%) showed broad-spectrum in vitro antimicrobial activity (inhibiting all three test strains), while 12 (34%) exhibited narrow spectrum activity against individual pathogens (seven as anti-staphylococcal and five as anti-candidal). Plants such as Alangium salviifolium, Antidesma bunius, Bauhinia racemosa, Careya arborea, Caseria graveolens, Cleistanthus patulus, Colebrookea oppositifolia, Crotalaria pallida, Croton roxburghii, Holarrhena pubescens, Hypericum gaitii, Macaranga peltata, Protium serratum, Rubus ellipticus, and Suregada multiflora showed strong antibacterial effects, whilst Alstonia scholaris, Butea monosperma, C. arborea, C. pallida, Diospyros malbarica, Gmelina arborea, H. pubescens, M. peltata, P. serratum, Pterospermum acerifolium, R. ellipticus, and S. multiflora demonstrated strong antifungal activity. Plants such as A. salviifolium, A. bunius, Aporosa octandra, Barringtonia acutangula, C. graveolens, C. pallida, C. patulus, G. arborea, H. pubescens, H. gaitii, Lannea coromandelica, M. peltata, Melastoma malabathricum, Millettia extensa, Nyctanthes arbor-tristis, P. serratum, P. acerifolium, R. ellipticus, S. multiflora, Symplocos cochinchinensis, Ventilago maderaspatana, and Wrightia arborea inhibit survival of C. elegans and could be a potential source for anthelmintic activity. Additionally, plants such as A. bunius, C. graveolens, C. patulus, C. oppositifolia, H. gaitii, M. extensa, P. serratum, R. ellipticus, and V. maderaspatana showed anti-enteroviral activity. Most of the plants, whose traditional use as anti-infective agents by the tribals was well supported, show in vitro inhibitory activity against an enterovirus, bacteria (E. coil, S. aureus), a fungus (C. albicans), or a nematode (C. elegans).

The chemokine receptor 4 (CXCR4) and 7 (CXCR7) are G-protein-coupled receptors involved in various diseases including human cancer. As such, they have become important targets for therapeutic intervention. Cell-based receptor assays, able to detect agents that modulate receptor activity, are of key importance for drug discovery. We evaluated the potential of cellular electric impedance for this purpose. Dose-dependent and specific stimulation of CXCR4 was detected upon addition of its unique chemokine ligand CXCL12. The response magnitude correlated with the CXCR4 expression level. Gαi coupling and signaling contributed extensively to the impedance response, whereas Gαq- and Gβγ-related events had only minor effects on the impedance profile. CXCR7 signaling could not be detected using impedance measurements. However, increasing levels of CXCR7 expression significantly reduced the CXCR4-mediated impedance readout, suggesting a regulatory role for CXCR7 on CXCR4-mediated signaling. Taken together, cellular electric impedance spectroscopy can represent a valuable alternative pharmacological cell-based assay for the identification of molecules targeting CXCR4, but not for CXCR7 in the absence of CXCR4.