Acute lung injury (ALI) and its more severe form, acute respiratory distress syndrome (ARDS) as common life-threatening lung diseases with high mortality rates are mostly associated with acute and severe inflammation in lungs. With increasing in-depth studies of ALI/ARDS, significant breakthroughs have been made, however, there are still no effective pharmacological therapies for treatment of ALI/ARDS. Especially, the novel coronavirus pneumonia (COVID-19) is ravaging the globe, and causes severe respiratory distress syndrome. Therefore, developing new drugs for therapy of ALI/ARDS is in great demand, which might also be helpful for treatment of COVID-19. Natural compounds have always inspired drug development, and numerous natural products have shown potential therapeutic effects on ALI/ARDS. Therefore, this review focuses on the potential therapeutic effects of natural compounds on ALI and the underlying mechanisms. Overall, the review discusses 159 compounds and summarizes more than 400 references to present the protective effects of natural compounds against ALI and the underlying mechanism.

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Asiatic acid (AA) is a naturally occurring aglycone of ursane type pentacyclic triterpenoids. It is abundantly present in many edible and medicinal plants including Centella asiatica that is a reputed herb in many traditional medicine formulations for wound healing and neuropsychiatric diseases. AA possesses numerous pharmacological activities such as antioxidant and anti-inflammatory and regulates apoptosis that attributes its therapeutic effects in numerous diseases. AA showed potent antihypertensive, nootropic, neuroprotective, cardioprotective, antimicrobial, and antitumor activities in preclinical studies. In various in vitro and in vivo studies, AA found to affect many enzymes, receptors, growth factors, transcription factors, apoptotic proteins, and cell signaling cascades. This review aims to represent the available reports on therapeutic potential and the underlying pharmacological and molecular mechanisms of AA. The review also also discusses the challenges and prospects on the pharmaceutical development of AA such as pharmacokinetics, physicochemical properties, analysis and structural modifications, and drug delivery. AA showed favorable pharmacokinetics and found bioavailable following oral or interaperitoneal administration. The studies demonstrate the polypharmacological properties, therapeutic potential and molecular mechanisms of AA in numerous diseases. Taken together the evidences from available studies, AA appears one of the important multitargeted polypharmacological agents of natural origin for further pharmaceutical development and clinical application. Provided the favorable pharmacokinetics, safety, and efficacy, AA can be a promising agent or adjuvant along with currently used modern medicines with a pharmacological basis of its use in therapeutics.

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Triterpenoids are the most representative group of phytochemicals, as they comprise more than 20,000 recognized molecules. These compounds are biosynthesized in plants via squalene cyclization, a C30 hydrocarbon that is considered to be the precursor of all steroids. Due to their low hydrophilicity, triterpenes were considered to be inactive for a long period of time; however, evidence regarding their wide range of pharmacological activities is emerging, and elegant studies have highlighted these activities. Several triterpenic skeletons have been described, including some that have presented with pentacyclic features, such as oleanolic and ursolic acids. These compounds have displayed incontestable biological activity, such as antibacterial, antiviral, and antiprotozoal effects, which were not included in a single review until now. Thus, the present review investigates the potential use of these triterpenes against human pathogens, including their mechanisms of action, via in vivo studies, and the future perspectives about the use of compounds for human or even animal health are also discussed.

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Endophytes are microbes that inhabit host plants without causing disease and are reported to be reservoirs of metabolites that combat microbes and other pathogens. Here we review diverse classes of secondary metabolites, focusing on anti-microbial compounds, synthesized by fungal endophytes including terpenoids, alkaloids, phenylpropanoids, aliphatic compounds, polyketides, and peptides from the interdisciplinary perspectives of biochemistry, genetics, fungal biology, host plant biology, human and plant pathology. Several trends were apparent. First, host plants are often investigated for endophytes when there is prior indigenous knowledge concerning human medicinal uses (e.g., Chinese herbs). However, within their native ecosystems, and where investigated, endophytes were shown to produce compounds that target pathogens of the host plant. In a few examples, both fungal endophytes and their hosts were reported to produce the same compounds. Terpenoids and polyketides are the most purified anti-microbial secondary metabolites from endophytes, while flavonoids and lignans are rare. Examples are provided where fungal genes encoding anti-microbial compounds are clustered on chromosomes. As different genera of fungi can produce the same metabolite, genetic clustering may facilitate sharing of anti-microbial secondary metabolites between fungi. We discuss gaps in the literature and how more interdisciplinary research may lead to new opportunities to develop bio-based commercial products to combat global crop and human pathogens.

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There is growing use of anticancer complementary and alternative medicines (CAMs) worldwide. The purpose of the current study is to assess a sizeable variety of natural and plant sources of diverse origin, to ascertain prospective research directives for cancer treatment and potential new chemotherapy drug sources. In this study, 374 natural extracts (10 microg/mL-5 mg/mL) were evaluated for dose-dependent tumoricidal effects using immortal neuroblastoma of spontaneous malignant origin. The findings indicate no pattern of tumoricidal effects by diverse plants with similar families/genus under the classes Pinopsida, Equisetopsida, Lycopodiosida, Filicosida, Liliopsida Monocotyledons or Magnoliopsida Dicotyledons. The results indicate that many of the most commonly used CAMs exhibited relatively weak tumoricidal effects including cats claw, astragalus, ginseng, echinacea, mistletoe, milk thistle, slippery elm, cayenne, chamomile, don quai, meadowsweet, motherwort and shepherd's purse. The data demonstrate that the most potent plant extracts were randomly dispersed within the plantae kingdom (LC(50) = 31-490 microg/mL) in order of the lowest LC(50) Dioscorea villosa (Dioscoreaceae) > Sanguinaria canadensis (Papaveraceae) > Dipsacus asper (Dipsacaceae) > Populus balsamifera (Salicaceae) > Boswellia carteri (Burseraceae) > Cyamopsis psoralioides (Fabaceae) > Rhamnus cathartica (Rhamnaceae) > Larrea tridentate (Zygophyllaceae) > Dichroa febrifuga (Hydrangeaceae) > Batschia canescens (Boraginaceae) > Kochia scoparia (Chenopodiaceae) > Solanum xanthocarpum (Solanaceae) > Opoponax chironium (Umbelliferae) > Caulophyllum thalictroides (Berberidaceae) > Dryopteris crassirhizoma (Dryopteridaceae) > Garcinia cambogia (Clusiaceae) > Vitex agnus-castus (Verbenaceae) > Calamus draco (Arecaceae). These findings show tumoricidal effect by extracts of wild yam root, bloodroot, teasel root, bakuchi seed, dichroa root, kanta kari, garcinia fruit, mace, dragons blood and the biblically referenced herbs: balm of gilead bud, frankincense and myrrh gum.

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