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.

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.

The prevention of disease and infection requires immune systems that operate effectively. This is accomplished by the elimination of infections and abnormal cells. Immune or biological therapy treats disease by either stimulating or inhibiting the immune system, dependent upon the circumstances. In plants, animals, and microbes, polysaccharides are abundant biomacromolecules. Due to the intricacy of their structure, polysaccharides may interact with and impact the immune response; hence, they play a crucial role in the treatment of several human illnesses. There is an urgent need for the identification of natural biomolecules that may prevent infection and treat chronic disease. This article addresses some of the naturally occurring polysaccharides of known therapeutic potential that have already been identified. This article also discusses extraction methods and immunological modulatory capabilities.

Coronavirus pneumonia is accompanied by rapid virus replication, where a large number of inflammatory cell infiltration and cytokine storm may lead to acute lung injury, acute respiratory distress syndrome (ARDS) and death. The uncontrolled release of pro-inflammatory cytokines, including interleukin (IL)-1β and IL-6, is associated with ARDS. This constituted the first study to report on the variability in physicochemical properties of β-glucans extracts from the same edible mushroom Lentinus edodes on the reduction of these pro-inflammatory cytokines and oxidative stress. Specifically, the impact on the immunomodulatory and cytoprotective properties of our novel in ‘house’ (IH-Lentinan, IHL) and a commercial (Carbosynth-Lentinan, CL) Lentinan extract were investigated using in vitro models of lung injury and macrophage phagocytosis. CL comprised higher amounts of α-glucans and correspondingly less β-glucans. The two lentinan extracts demonstrated varying immunomodulatory activities. Both Lentinan extracts reduced cytokine-induced NF-κB activation in human alveolar epithelial A549 cells, with the IHL extract proving more effective at lower doses. In contrast, in activated THP-1 derived macrophages, the CL extract more effectively attenuated pro-inflammatory cytokine production (TNF-α, IL-8, IL-2, IL-6, IL-22) as well as TGF-β and IL-10. The CL extract attenuated oxidative stress-induced early apoptosis, while the IHL extract attenuated late apoptosis. Our findings demonstrate significant physicochemical differences between Lentinan extracts, which produce differential in vitro immunomodulatory and pulmonary cytoprotective effects that may also have positive relevance to candidate COVID-19 therapeutics targeting cytokine storm.

β-glucans are a large class of complex polysaccharides found in abundant sources. Our dietary sources of β-glucans are cereals that include oats and barley, and non-cereal sources can consist of mushrooms, microalgae, bacteria, and seaweeds. There is substantial clinical interest in β-glucans; as they can be used for a variety of diseases including cancer and cardiovascular conditions. Suitable sources of β-glucans for biopharmaceutical applications include bacteria, microalgae, mycelium, and yeast. Environmental factors including culture medium can influence the biomass and ultimately β-glucan content. Therefore, cultivation conditions for the above organisms can be controlled for sustainable enhanced production of β-glucans. This review discusses the various sources of β-glucans and their cultivation conditions that may be optimised to exploit sustainable production. Finally, this article discusses the immune-modulatory potential of β-glucans from these sources.