Jacques Cartier, a French explorer, and his crew had first used pine bark extract in 1535 for fighting against lethal scurvy disease, which occurs due to vitamin C deficiency. They had ingested herbal tea made up of pine bark extract. This practical experience had proven pine bark extract composition either have similar functioning like vitamin C or enhance this vitamin level in the body. Jacques Cartier had mentioned this experience in his book. Later Jacques Masquelier had identified pycnogenol, oligomeric proanthocyanidin, the active constituents of pine bark extract.
South and southwest of China are the native places of Pinus massoniana. Turpentine, the active constituent of Pinus massoniana has used in traditional Chinese medicine for the treatment of arthralgia, hemorrhage, inflammation, rheumatism, and cancer. 
Previously pine bark extract is considered a non-convenient waste product produced in the timber industry. But the presence of natural polyphenols made pine bark extract as a potential health beneficial product that has nutritional, and medicinal properties. Both Pinus radiata and Pinus massoniana contain pycnogenol, as a primary bioactive phytochemical. Another phytochemical present in pine bark extract is Enzogenol. Both Enzogenol and pycnogenol are also available as supplements. [1,2]
Pycnogenol and Enzogenol present in Pine bark extract have a protective effect against oxidative stress, as they act as free radical quenchers. Pycnogenol has a lipid peroxidation inhibitory effect and also regenerates the ascorbyl radical. It helps to maintain glutathione and vitamin E endogenously and prevents oxidative damage. Both of these phytochemicals can inhibit the thiobarbituric acid reactive product generation and oxidative hemolysis by hydrogen peroxide.
Pine bark extract also has anti-inflammatory properties. An animal study confirmed that Pycnogenol can inhibit antidinitrophenyl (DNP) IgE–mediated passive cutaneous anaphylaxis, reduces histamine release, and other inflammatory mediators like tumor necrosis factor-α and IL-6. Pycnogenol can control mast cell activation.
Pine bark extract cyclooxygenase (COX)-2 and 5-lipoxygenase gene expression and reduces leukotriene biosynthesis which also effective to exert anti-inflammatory and analgesic effect.
The anticancer effect of obtaining due to Pinus massoniana bark extract promotes cell cycle arrest by interfering with the G1 and S phase and activates immune functioning against cancer cells.
Pycnogenol has a significant antihypertensive effect due to its potent antioxidant property provides a protective effect against endothelial dysfunction and also exerts vasorelaxation by activation of endothelial nitric oxide synthesis.
Oxidative stress damages the proteinous structure. Pycnogenol prevents the accumulation of damaged proteins in the brain and also protects the nerve cells against β-amyloid in glutamate-induced toxicity. [1,2]
The recommended dose of pine bark extract is 20–100 mg/day for long-term application and 100–300 mg for short term treatment. Pine bark extract usually collected from Pinus radiata and Pinus massoniana, the two species of Pinus genera. Pycnogenol and Enzogenol containing herbal products are also available in the herbal medicinal system. 
Toyo Shinyaku, a Japanese drug manufacturing company formulate Flavangenol®, a pine bark extract containing herbal regimen. 
Pycnogenol has different medicinal properties like antioxidant, anti-inflammatory, anticancer, cardioprotective, and neuroprotective properties. Pycnogenol present in pine bark extract is used as a nutritional supplement because this phytochemical has a remedial effect on circulatory dysfunction, chronic inflammatory condition, and asthma. Pine bark extract can inhibit migraine and cancer cell growth. 
UV radiation exposure is a common skin tissue damaging factor. Prolong and chronic exposure to UV- light generates free radicals in skin tissue and one of the major cause of photoaging. Pine bark extract containing Pycnogenol protects skin from UV damage and may effective to protect against photoaging. It is also expected that Pine bark extract can prevent free radical-induced skin damage. 
Pine bark extract reduces lipid peroxidation by enhancing endogenous antioxidant enzyme activity. Thus it gives from permanent damage due to free radicals burden. A combination of vitamin C with Enzogenol is an effective remedial measure to reduced systemic plasma protein oxidation, which helps to overall health benefits. Accumulation of free radicals in the systemic circulation may cause DNA, lipids, and protein damage and leads to chronic cerebral, cardiovascular, and metabolic diseases. 
The anti-inflammatory and histamine release the suppressive effect of Pine bark extract can effective to treat the allergic inflammatory condition and also prevent anaphylaxis. 
Asthma patients can be benefited by inhaling Pine bark extract formulation as it down-regulates 5-lipoxygenase and concurrently leukotriene levels also reduced in asthmatic patients. Experts considered Pycnogenol may be a promising treatment of asthma, as they expected a combination of Pycnogenol with corticosteroids able to reduce dosage and frequency of inhalation corticosteroid and also potentially reduces asthma attack. 
Pycnogenol, the bioactive phytochemical of Pine bark extract can alleviate pain and stiffness associated with arthritis and osteoarthritis due to its anti-inflammatory properties. Researchers expected Pycnogenol is a promising anti-arthritic drug candidate.
Autoimmune disease treatment
Autoimmune disease conditions like type I allergies, asthma, and arthritis can be controlled by Pinus massoniana bark extract due to its anti-inflammatory properties and immunomodulatory effects with minimum side effects. 
Both Pinus massoniana bark extract and Pycnogenol treatment help to control micro-organism causing infection. Pinus massoniana bark extract provides protection against Epstein-Barr virus causing infections like nasopharyngeal carcinoma by interfering with life cycle stages of this virus. Whereas, Pycnogenol is effective against human immunodeficiency virus type-1 and Helicobacter pylori causing infections by up-regulating endogenous antioxidant level. The suppression of Helicobacter pylori helps to prevent gastric ulcers.
Both Pinus massoniana bark extract and Pycnogenol have anticancer properties by regulating carcinogens, anti mutation properties, and tumor migration. Pinus massoniana bark extract exerts apoptosis-inducing activity in the cancer cell with very little effect on normal cell structure. Pycnogenol provides symptomatic relief from radiotherapy and chemotherapy including alleviation of chemotherapy-induced nausea, vomiting, diarrhea, and weight loss; radiotherapy-induced mouth and throat ulcer, eye, and mouth dryness. 
A double-blind, placebo-controlled, randomized, parallel trial reported that a pine bark extract formulation known as Flavangenol® might minimize the risk of cardiovascular disease in patients having obesity, prehypertension, and insulin insensitivity. This study aimed to test the blood pressure-lowering effect, improvement of glycemic control, liver function and plasma lipoprotein profile and body weight management, antioxidant profile, anti-inflammatory property, and alter blood coagulation factor of this formulation. 
Type 1 diabetes-associated enhanced thromboxane synthesis induces thrombosis, which leads to cardiovascular disorders. Long-term treatment with Pycnogenol exerts antithrombotic effects by lowering platelet hyperactivity. Thus, pine bark extract helps to reduce the risk of diabetes-associated cardiovascular complications. 
Pycnogenol present in pine bark extract has vasorelaxant activity by acting on the endothelial cell. Intake of pine bark extract containing Pycnogenol with a dose of 100mg/ day can reduce the dosage of the calcium channel blocker nifedipine, and helps to keep normal blood pressure. 
Fatty liver treatment
Pycnogenol prevents fat accumulation in the liver by suppressing adipose differentiation-related protein (ADRP) expression. This helps to treat the fatty liver condition. 
The antioxidant property of pine bark extract due to the presence of Pycnogenol is effective to provide better diabetes control in patients with type 2 diabetes mellitus. 
Pine bark extract and vitamin C combination help to reduce migraines due to their potent antioxidant properties. 
Improve cognitive performance
Pine bark extract containing Enzogenol improves working memory or short term memory. A research published article showed a reported combination of Enzogenol and vitamin C improves immediate recognition tasks. The antioxidant property, blood circulation improvement in the brain tissues due to the presence of Enzogenol improves cognitive functioning. 
Prevent neurodegenerative diseases
Pine bark extract containing Pycnogenol may reduce the risks of neurodegenerative diseases, such as Parkinson’s, Alzheimer’s, and Huntington’s disease due to its neuroprotective action. 
Daily intake of Pycnogenol helps to provide symptomatic relief from the menopausal syndrome, such as insomnia or sleep disturbances, etc. 
Mild to moderate dose of Pine bark extract is safe to use. However, some reported side effects are nausea, gastrointestinal discomfort, headache, and dizziness. The higher dose of Enzogenol can also cause some adverse effects like diarrhea and emesis. 
It is advised not to take Pine bark extract during pregnancy and lactation.