Biological Applications of Algae in Osteogenic Therapies: A Review of Recent Advances

ABSTRACT

The microalgae, like Chlorella, Spirulina, and various genera of red and brown algae, contain other beneficial bioactive compounds, such as polysaccharides, proteins, vitamins, and minerals, that may promote owning formation. This article looks at how bioactive compounds derived from algae contribute to the process of bone mitosis and how they modulate inflammation as well as activate signals associated with bone remodeling. The review states that despite the promise, algae for osteogenic therapies requires further study for ordinary data and fundamental knowledge in therapeutic treatments that should be highly specialized.

INTRODUCTION

Bones contribute to general well-being since they are both the framework of the body and a protector of organs while also being a primary means of transportation regarding the individual’s body. However, diseases, such as osteoporosis, bone fractures, and other bone disorders, remain a challenge to persons and healthcare systems worldwide.[1,2] Traditional approaches that are normally used include chemical treatments like bisphosphonates or hormonal treatments like estrogen replacement therapy, but these come with problems like side effects or reduce efficacy after long-term use.[3,4] Global biochemical characteristics of algae have several potential benefits for revolutionary osteogenic treatments.[5,6] Bioactive polysaccharides have the potential to stimulate both the osteoblast proliferation and differentiation and to suppress the osteoclast activity.[7] In addition, algae also contain calcium and magnesium which are important for bone density.[8] The structural composites belong to these groups. Additionally, since the extract of algae possesses an anti-inflammatory compound to decrease the inflammation of osteoporosis-related to bone loss, it may help to encourage a higher environment for bone healing and remodeling.[9] Ultimately, algae show possibilities in osteogenic therapy, although their influences are still not quite clear.[10,11]

ALGAE AND THEIR BIOACTIVE COMPOUNDS

Chlorella is abundant in proteins, vitamins, and minerals, and is also a source of chlorophyll, carotenoids, and complex sugar.[12] It shows a high concentration of phycocyanin. Anti-inflammatory qualities could potentially promote a beneficial setting for repairing bones. Macroalgae are sizable, multicellular algae categorized into three primary groups: green, brown, and red algae. Green algae Ulva are abundant in vitamins A, C, E, and K, as well as minerals. They comprise polysaccharides, such as ulvan, which may possess anti-inflammatory and osteogenic characteristics.[13] Brown algae Fucus and Laminaria are notably abundant in alginates, fucoidan, and polyphenols. Fucoidan has been demonstrated to enhance osteoblast differentiation and suppress osteoclast activity.[14] Red algae, such as Porphyra and Gracilaria, encompass carrageenan and phycoerythrin, both of which exhibit antioxidant and anti-inflammatory characteristics. These chemicals may promote osteogenesis and bolster overall skeletal health.[15] Cyanobacteria are photosynthetic bacteria that exhibit traits of both bacteria and algae. They are recognized for their capacity to generate oxygen and assimilate nitrogen. Arthrospira platensis (Spirulina) Bioactive constituents algae include a plethora of bioactive chemicals that can aid in osteogenic therapies.[16]

MECHANISMS OF ACTION OF ALGAL BIOACTIVE COMPOUNDS IN OSTEOGENESIS

Algal bioactive compounds affect osteogenesis which is listed in Table 1 mainly through several coupled pathways that act on osteoblasts and osteoclasts cells. Knowledge of these mechanisms is instrumental in designing therapeutic interventions for bone-related diseases.[23]

Table 1.

Mechanisms of action of algal bioactive compounds in bone treatment

Bioactive compound	Algae	Mechanisms of action	Effects on bone health
Fucoidan	Brown algae (Fucus, Laminaria)	Stimulates osteoblast differentiation Inhibits osteoclast activity Enhances mineralization	Promotes bone formation Reduces bone resorption.[17]
Omega-3 fatty acids	Microalgae (Spirulina, Chlorella)	Modulates inflammatory and cytokines Enhances calcium absorption  Supports osteoblast function	Improves bone density Reduces inflammation-related bone loss.[18]
Calcium	Various algae (macro and micro)	Provides essential mineral for bone formation Enhances osteoblast activity	Essential for maintaining bone density and strength[19]
Carrageenan	Red algae (Porphyra, Gracilaria)	Supports cell signaling pathways Promotes osteogenic differentiation	Aids in bone healing and regeneration[20]
Phycocyanin	Blue–green algae (Aphanizomenon)	Antioxidant properties Modulates osteogenic genes	Protects bone cells from oxidative stress Promotes bone regeneration[21]
Alginates	Brown algae (Laminaria, Fucus)	Binds to minerals and increases their bioavailability, anti-inflammatory effects	Enhances calcium absorption Reduces inflammation-induced bone loss[22]

Stimulation of osteoblast proliferation and differentiation

Osteoblasts are the cells that are responsible for the formation of bone.

Growth Factor Production: Algal polysaccharides found in Chlorella and Spirulina literature have been reported to release growth factors, such as BMPs and VEGF. These factors enhance osteoblast activity and facilitate angiogenesis. Algal chemicals can activate critical signaling pathways associated with osteogenesis, such as the Wnt/β-catenin pathway. The activation of this pathway results in heightened expression of osteogenic markers, such as osteocalcin and alkaline phosphatase. Bioactive chemicals in algae can facilitate the mineralization process by stimulating hydroxyapatite deposition, the principal mineral component of bone. This is frequently evaluated using in vitro investigations that quantify the mineralization of extracellular matrices produced by osteoblasts.[24]

Modulation of osteoclast activity

Osteoclasts facilitate bone resorption. The equilibrium between osteoblast and osteoclast activity is crucial for sustaining bone health. Algal bioactive substances can influence osteoclastogenesis and activity via multiple mechanisms[25] Inhibition of RANK/RANKL Signaling: The receptor activator of nuclear factor kappa-B (RANK) and its ligand (RANKL) are essential for the differentiation and activation of osteoclasts. Specific algal extracts can impede RANKL signaling, hence diminishing osteoclast development and activity. Fucoidan extracted from brown algae has demonstrated the ability to inhibit RANKL-induced osteoclastogenesis.

Decrease in Inflammatory Mediators: Chronic inflammation significantly contributes to heightened osteoclast activity and subsequent bone loss. Algal bioactive substances possess anti-inflammatory effects that can diminish the levels of pro-inflammatory cytokines, such as TNF-α and IL-6, which facilitate osteoclast genesis. This reduction facilitates a more favorable bone remodeling environment.[25]

Anti-inflammatory effects

Inflammation can impede bone repair and regeneration. Algal extracts contain chemicals with anti-inflammatory effects that can enhance osteogenic processes.

Antioxidants algal-derived antioxidants, including carotenoids and polyphenols, assist in alleviating oxidative stress, which may result in inflammation and cellular damage. These chemicals safeguard osteoblasts by neutralizing free radicals and fostering an environment suitable to bone production.[26]

Cytokine Modulation: Bioactive chemicals in algae can regulate the expression of several cytokines associated with inflammation. Certain polysaccharides can suppress the expression of inflammatory cytokines, hence diminishing inflammation and facilitating bone repair.

ENHANCEMENT OF MINERAL HOMEOSTASIS

Bioactive chemicals from algae play a crucial role in sustaining mineral homeostasis, essential for bone health. Numerous algae possess a natural abundance of calcium and magnesium, vital nutrients for bone composition and density. Algal ingestion can enhance dietary mineral intake, therefore promoting bone health.[24] Calcium derived from algae is frequently more accessible than other dietary sources, indicating enhanced absorption and utilization by the body. This improves its efficacy in facilitating bone mineralization.

PROMOTION OF ANGIOGENESIS

Bone regeneration necessitates sufficient vascularization to supply nutrients and eliminate waste wastes. Algal extracts can stimulate angiogenesis, which is crucial for effective bone repair.[27]

Algal chemicals can enhance the synthesis of VEGF, a crucial factor that facilitates angiogenesis. Enhanced angiogenesis facilitates improved nutrition supply to osteoblasts and promotes the overall healing process. Certain studies indicate that algal extracts may promote the proliferation and migration of endothelial cells, essential for angiogenesis.[27]

PRECLINICAL AND CLINICAL STUDIES

Preclinical studies

Multiple studies have proven the beneficial impacts of algal extracts on bone health in animal models. In comparing the effects of fucoidan obtained from brown algae, it has been shown that it resulted in increased bone density and mineralization in the ovariectomized rat model of postmenopausal bone loss.[1] They have found that Spirulina increases bone mineral density and osteoblast activity in osteoporotic mice.[14]

Clinical Studies

Research in the use of algae in clinical setting for bone healing and reconstructive surgery is, however, still in its infancy. In the present studies, various publications described that algal extricates and their components can enhance the bone status and stimulate osteogenesis in various clinical settings. A placebo-controlled crossover trial examined the effects of Spirulina intervention on postmenopausal women with a family history of osteoporosis. For the six-month trial, participants received their daily doses of Spirulina.[19] The improvements depicted were increases in the BMD of the lumbar spine and femoral neck in the Spirulina group compared with the control group. The researchers attributed this impact on the other hand to the possibility of increased calcium, and Vitamin K which is recognized for its benefits on bones.

A clinical trial evaluated the effects of Chlorella supplementation on individuals receiving therapy for osteoporosis. Participants ingested Chlorella for a duration of three months while maintaining their prescription medications. The results indicated a significant decrease in bone turnover indicators, such as osteocalcin, in those consuming Chlorella, implying a possible regulatory influence on bone metabolism.[28] Brown algae, especially those abundant in fucoidan, have garnered attention for their anti-inflammatory and osteogenic attributes. A randomized clinical trial assessed the impact of fucoidan supplementation on individuals with osteoporosis. Participants were administered fucoidan capsules for a duration of six months.[3] The impacts of carrageenan, a polysaccharide derived from red algae, have been investigated in clinical environments[29] Results demonstrated that carrageenan supplementation facilitated improved bone repair in patients with fractures.[29,30]

CONCLUSION

This research of algae for osteogenic treatments can be a new chance to improve the quality of bone disease and injuries, like osteoporosis and fracture fixations. Consequently, this systematic review integrates available literature regarding the several types of algae with specific focus on their bioactive chemicals for bone formation. Algae contain ingredients, such as polysaccharides, proteins, vitamins, and minerals, all of which enhance their ability to support new bone formation.[31] It was also observed that the extracts of algae possess anti-inflammatory effects that help to control, without fail, chronic inflammation that is vital in preserving bone mass and promoting healing.[12] While numerous in vitro/in vivo studies have demonstrated the potential of algae-derived compounds and sources in osteogenic treatments, few clinical uses have been explored.[32,33,34] It is thus important to have integrated clinical trials performed in several clinical centers to identify the right doses, types of pharmaceuticals, and temporal schedules for different subgroups of patients. Furthermore, efficacy necessitates the standardization; the content of these extracts is heterogeneous. Standardization is required for homogeneity of treatment results in algae therapy integrated with osteogenic therapy may offer a natural, economic supplement or substitute to the present medications.[35] Currently, growing studies are showing the pharmacological benefits of bioactive compounds in algae, establishing a potentiality for the new alga-derived drugs for solving the complex nature of bone health challenges.[36,37] It can therefore be indicated that algae offer a promising way in search of efficient treatment for bone-associated diseases.[38,39]

Conflicts of interest

There are no conflicts of interest.

Funding Statement

Nil.