β-glucans are complex polysaccharides that are found in several plants and foods, including mushrooms. β-glucans display an array of potentially therapeutic properties. β-glucans have metabolic and gastro-intestinal effects, modulating the gut microbiome, altering lipid and glucose metabolism, reducing cholesterol, leading to their investigation as potential therapies for metabolic syndrome, obesity and diet regulation, gastrointestinal conditions such as irritable bowel, and to reduce cardiovascular and diabetes risk. β-glucans also have immune-modulating effects, leading to their investigation as adjuvant agents for cancers (solid and haematological malignancies), for immune-mediated conditions (e.g., allergic rhinitis, respiratory infections), and to enhance wound healing. The therapeutic potential of β-glucans is evidenced by the fact that two glucan isolates were licensed as drugs in Japan as immune-adjuvant therapy for cancer in 1980. Significant challenges exist to further clinical testing and translation of β-glucans. The diverse range of conditions for which β-glucans are in clinical testing underlines the incomplete understanding of the diverse mechanisms of action of β-glucans, a key knowledge gap. Furthermore, important differences appear to exist in the effects of apparently similar β-glucan preparations, which may be due to differences in sources and extraction procedures, another poorly understood issue. This review will describe the biology, potential mechanisms of action and key therapeutic targets being investigated in clinical trials of β-glucans and identify and discuss the key challenges to successful translation of this intriguing potential therapeutic.

• β-Glucans from shiitake mushroom reduces IL-1β, IL-6 in in vitro lung injury model. • β-Glucans from same source can differ in immunomodulatory and pulmonary cytoprotective effects. • β-Glucans can reduce oxidative stress and activate macrophages. • β-Glucans may ameliorate cytokine storm that causes ARDS as seen with COVID-19.

The inclusion of physiologically active molecules into a naturally occurring polymer matrix can improve the degradation, absorption, and release profile of the drug, thus boosting the therapeutic impact and potentially even reducing the frequency of administration. The human body produces significant amounts of polysaccharide hyaluronic acid, which boasts exceptional biocompatibility, biodegradability, and one-of-a-kind physicochemical features. In this review, we will examine the clinical trials currently utilizing hyaluronic acid and address the bright future of this versatile polymer, as well as summarize the numerous applications of hyaluronic acid in drug delivery and immunomodulation.

Bacterial infection remains the main cause of acute respiratory distress syndrome and is a leading cause of death and disability in critically ill patients. Here we report on the use of purified β‐glucan (lentinan) extracts from Lentinus edodes (Shiitake) mushroom that can reduce infection by a multidrug‐resistant clinical isolate of Klebsiella pneumoniae in a rodent pneumonia model, likely through immunomodulation. Adult male Sprague–Dawley rats were subjected to intra‐tracheal administration of K. pneumoniae to induce pulmonary sepsis and randomized to three groups; vehicle control (Vehicle, n = 12), commercial lentinan (CL, n = 8) or in‐house extracted lentinan (IHL, n = 8) were administered intravenously 1 h postinfection. Physiological parameters and blood gas analysis were measured, bacterial counts from bronchoalveolar‐lavage (BAL) were determined, along with differential staining of white cells and measurement of protein concentration in BAL 48 h after pneumonia induction. Use of IHL extract significantly decreased BAL CFU counts. Both CL and IHL extractions reduced protein concentration in BAL. Use of IHL resulted in an improvement in physiological parameters compared to controls and CL. In conclusion, administration of lentinan to treat sepsis‐induced lung injury appears safe and effective and may exert its effects in an immunomodulatory manner.

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