Formation of central nervous system (CNS) network requires active axonal elongation and systematic explorations activity of environment by growing of axons in order to be directed to their correct target [1
]. Neuronal cells are able to sense the surrounding and form branches in response to molecular information from extracellular milieu that instruct the maturation process and induce neurite regeneration in pathological situations such as trauma or degenerative diseases [1
]. Neurite outgrowth in cultured neurons is considered as an indication of neuroregenerative potential [2
Extension and remodeling of neurites play essential roles in development and neuronal plasticity regulated by neuroserpin [3
]. Cultured rat pheochromocytoma PC-12 cells have been used extensively as an in vitro
model system for investigation of neuronal differentiation. Epidermal growth factor (EGF) and nerve growth factor (NGF) both activate extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase (MAPK) [4
]. But PC-12 cells only respond to neurotrophin NGF and differentiate into sympathetic neuron phenotype and extending axon-like processes called neurites [3
]. This serves as an excellent model to study the effects of molecules both synthetic and natural that will stimulate the outgrowth of neurites.
Of the many diseases that threaten humans, neurodegenerative diseases can be very traumatic as one ages. Neurohealth is the concern for the predicted silver tsunami to hit humans—the aging tsunami is projected to be 80–90 million of 65-plus population in 2050 [5
]. Why the concern? Alzheimer and neurogenerative diseases are high on the list of chronic diseases of the aged. Alzheimer's disease is primarily a disorder of aging with loss of cognitive function. This disease is characterized biologically by the death of neurons in the forebrain, hippocampus, and cerebral cortex accompanied by the presence of amyloid deposition.
Many of the drugs in the market only delay further deterioration and do not reverse the damage done to cognitive functions. The search is now for small molecules that can cross the brain-blood and induce the production of nerve growth factor (NGF), a family of proteins responsible for maintenance, survival, and regeneration of neurons during adult life. It has been shown that NGF absence causes an Alzheimer's like symptoms in the adult brain of mice. We may have to turn to nature to prevent or reduce the severity of nerve-related diseases as we age. Prevention will be definitely better than cure. Many plants and spices such as turmeric are said to help. For example, in India, it is noted that Alzheimer among the older generation is not in alarming numbers. The regular consumption of spices including turmeric and pepper may be the reason and currently this is actively been studied. Currently mushrooms are also being investigated as sources of NGF stimulators.
Mushroom, a macrofungus that has either culinary or medicinal properties, has a visible fruiting body. Culinary mushrooms have been known as famous appetizing and nutritious food all over the world. Historically, medicinal mushrooms used by different tribes are best documented in the eastern world.
In Malaysia, several macrofungi are used by the Malays, Chineses, and indigenous communities for treatment of variety ailments. Lignosus rhinocerus
has been singled out as one of the most potent mushrooms for medicinal purposes dating to the 1700s by Tuan Haji Mat Yusop, a Malay in Pahang [6
]. Lignosus rhinocerus
is a unique “National Treasure” that can only be found in a small geographic region encompassing South China, Thailand, Malaysia, Indonesia, Philippines, Papua New Guinea, New Zealand, and Australia [6
]. Lignosus rhinocerus
(Cooke) Ryvarden is also known as “cendawan susu rimau” in Malay language or Tiger's Milk mushroom in English. The medicinal properties recorded by ethno-mycological surveys are yet to be validated scientifically.
has more than 15 medicinal uses. Different natives use it as an antipruritic, antipyretic, general tonic, starve off hunger, cancer, food poisoning, swollen breasts [7
], fever, cough, asthma, wound healing, and others [6
]. Although this mushroom has been recorded to have a number medicinal properties, usage is limited due to unavailability of the mushroom. The underground fungus tuber or sclerotium is the part with medicinal value and it can only be noticed when the fruiting body sprouts out from the ground when nature calls. Recently, efforts made to cultivate this medicinal mushroom have been successful [8
] and the mushrooms are now available for scientific studies.
The aim of the study was to assess the presence of active agents in aqueous extract of L. rhinocerus sclerotium that can stimulate neurite outgrowth in PC-12 and the enhancement of neurite outgrowth with the combination of NGF and aqueous extract in PC-12 cells. Quantitative morphological methods and neurofilament formation were used to study the differentiation effects on neurite outgrowth activities in PC-12 cell line. To our knowledge, this is the first report on the application of sclerotium of L. rhinocerus in neurite outgrowth stimulation activity.