Hepatoprotective activity

Hepatoprotective activity is the best known profile of action of S. chinensis fruit extracts and of individual dibenzocyclooctadiene lignans. The available literature contains many reports on scientific studies that confirm these properties of the fruit extracts. The most recent ones concern detailed studies on the mode of action of individual lignans. For example, the mechanism of action of gomisin A has been studied. It has been shown that it increases the microsomal activity of: cytochrome B5, P450, NADPH cytochrome C reductase, N-demethylase aminophenazone, 7-ethoxycoumarin O-deethylase, and reduces the activity of 3,4-dibenzopyrene hydroxylase. It also accelerates the proliferation of hepatocytes, the endoplasmic reticulum, and the hepatic flow (Panossian and Wikman 2008; World Health Organization 2007).

On the other hand, it has been demonstrated that the mechanism of the hepatoprotective action of γ-schisandrin is based on increasing the concentration of mitochondrial glutathione. It has also been shown that γ-schisandrin raises the concentration of vitamin C in the liver in test animals, which may also have an impact on its protective effect on hepatocytes and oxidation of lipids. Moreover, schisandrin B has been shown to protect against oxidative damage to liver tissues, too (Thandavarayan et al. 2015).

A recently conducted study on hepatoprotective effects of six schisandra lignans: gomisin A, schisandrin, deoxyschisandrin, schisandrin B, schisandrin C, and schisantherin A, on acetaminophen-induced liver injury has found that these effects are partially associated with the inhibition of cytochrome-mediated bioactivation. The results of morphological and biochemical assessment of this study demonstrated the protective effects of all the tested lignans against acetaminophen-induced liver injury. Among the investigated oxidative damage in liver, heart and exerted the strongest hepatoprotective effects (Jiang et al. 2015b).

Anti-inflammatory activity

The mechanism of anti-inflammatory action of schisandra lignans has been elucidated. It is based on the inhibition of the action of nitric oxide (NO) and the production of prostaglandins by stimulating the release of cyclooxygenase 2 (COX2) and inhibition of the expression of nitric oxide synthase (NOS) (Hu et al. 2014).

Antioxidative and detoxification activities

Studies on the antioxidative and detoxification mechanisms of action of dibenzocyclooctadiene lignans have shown that they inhibit microsomal lipid peroxidation, reduce the concentration of superoxide radicals, inhibit microsomal NADPH oxidation in hepatocytes and reduce the release of alanine aminotransferase (ALT) and lactate dehydrogenase, which increases membrane integrity and viability of hepatocytes (Yim et al. 2009). Moreover, the mechanism of protective, antioxidant and detoxifying action of lignans on hepatocytes is based on the increase in hepatic glutathione levels, and the activity of glutathione reductase and glutathione S-transferase (Miao et al. 2009). The latest studies have shown that schisandrin B attenuates doxorubicin induced cardiac dysfunction via antioxidative and anti-inflammatory effects. Schisandrin B has been shown to protect against oxidative damage in liver, heart and brain tissues in rodents (Chiu et al. 2008; Thandavarayan et al. 2015).

Anticancer activity

Anticancer activity of schisandra lignans has been studied in recent years. Researchers have been identifying the compounds responsible for this activity and studying its mechanisms. They have shown that gomisin A acts by inhibiting the production of the placental form of glutathione S-transferase (tumor marker) in hepatocytes and by increasing the excretion of the carcinogen; it also influences cytokinesis and reduces the number of focal neoplastic lesions in the liver. Other studies on gomisin A have shown anticancer activity on the colon carcinoma. It displayed apoptotic activity through caspase-7 cleavage in colon carcinoma HCT-116 cells (Hwang et al. 2011). A recent investigation concerned the effects of gomisin A on cancer cell proliferation and cell cycle arrest in HeLa cells. Gomisin A significantly inhibited cell proliferation, especially in the presence of tumour necrosis factor-α (TNF-α) (Waiwut et al. 2012).

In vitro studies on human leukemia cells—U973, it has been shown that another schisandra lignan—gomisin N, induces their apoptosis. The same mechanism of action of gomisin N has also been confirmed for hepatoma cells (Yim et al. 2009).

Apart from gomisin N, studies of the mechanism of anticancer action against two human tumor cell lines (adenocarcinoma cells—2008 and colon adenocarcinoma cells—LoVo) also included deoxyschisandrin. Both these lignans inhibited cell growth in a dose-dependent manner on both cell lines, but by inducing different types of cell death. In particular, deoxyschisandrin caused apoptosis in colon adenocarcinoma cells (LoVo) but not in ovarian adenocarcinoma cells (2008), while gomisin N induced apoptosis on both the cell lines used (Casarin et al. 2014).

As it turns out, the responsibility for the antitumor activity of the extracts from the fruits of S. chinensis is carried not only by dibenzocyclooctadiene lignans, but also by their polysaccharide fraction. A recent study confirmed the antitumor and immunomodulatory activities of water-soluble low-molecular-weight polysaccharide from S. chinensis (Zhao et al. 2013).

Immunostimulant activity

Research conducted in recent years has focused on studying the biological activity of the polysaccharide fraction from extracts of the fruits of S. chinensis. The immunostimulatory, immunomodulatory and antitumor action of water-soluble low-molecular-weight polysaccharide from S. chinensis has been proved. The polysaccharide fraction exhibited immunomodulating properties, such as improving the weight of immune organs, enhancing the phagocytic activity of peritoneal macrophages, promoting hemolysin formation, and increasing lymphocyte transformation (Chen et al. 2012; Zhao et al. 2013).

Influence on the central nervous system, adaptogenic and ergogenic activities

The dibenzocyclooctadiene lignans contained in the extract from the fruits of S. chinensis represent a group of natural chemical structures, which are now considered protectants against neuronal cell death and cognitive impairment in neurological disorders. In addition, the activity of polysaccharides contained in the fruits of S. chinensis is also studied in this respect. It has been shown that they, too, play an important role by raising the level of neurotransmitters in the central nervous system (Chen et al. 2012; Zhao et al. 2013).

Extracts from the fruits of S. chinensis are used in neurasthenia and states of exhaustion; they improve the ability to learn and memorize, indirectly increase alertness, improve concentration and mental performance. They are used as adjuvant substances in the treatment of Alzheimer’s, Parkinson’s, and Meniere’s diseases, and ADHD (attention deficit hyperactivity disorder). The fruit extracts exhibit antidepressant activity without inducing drowsiness (Jeong et al. 2013; Sa et al. 2015).

The fruits of S. chinensis have been recorded in some East Asian pharmacopoeias as an effective somnificant for the treatment of insomnia. However, the mechanism of the sedative and hypnotic effects of this plant raw material is still unclear. It has been shown that schisandrin—the dominant compound in S. chinensis fruit extract, produces beneficial sedative and hypnotic bioactivity, which might be mediated by the modification of the serotonergic system (Zhang et al. 2014a).

Moreover, adaptogenic and ergogenic properties of extracts from S. chinensis fruits were already well known from the traditional use of this plant. For this reason, S. chinensis, besides such plant species as Eleutherococcus senticosus, Panax ginseng, Panax quinquefolius or Rhodiola rosea, is classified as one of the worldwide known adaptogenic raw material (Winston and Maimes 2007).

Influence on the respiratory system

The most recent studies of the pharmacological properties of S. chinensis fruit extracts have reported a beneficial role in the treatment of some respiratory system disorders.

Data from 2014 suggest that S. chinensis fruit extracts have possible application as an antiasthmatic drug because they lower airway hyperresponsiveness, immunoglobuline E level, and immune cell infiltration in mice with asthma. The results also suggest that the fruit extracts could be used as a complementary or alternative medicine to glucocorticoids (Kim et al. 2014a).

It has also been shown that extracts from the fruits of S. chinensis reduce cough frequency and pulmonary inflammation in cough hypersensitivity induced in guinea pigs by exposure to cigarette smoke. Lignans were indicated as the compounds likely to be responsible for this effect (Zhong et al. 2015).

Influence on the cardiovascular system

Recently, S. chinensis fruit extracts and the dibenzocyclooctadiene lignans contained in them have gained attention for their potential role in the treatment of cardiovascular diseases, such as hypertension and myocardial infarction (Alexander and Wang 2012; Chun et al. 2014; Park et al. 2012a), which corroborates the observed effects of this species in traditional settings. Scientific investigations of the molecular mechanisms behind the observed phenomena have revealed that S. chinensis fruit extracts and its lignans exert cardiovascular protective activity by controlling multiple signalling pathways involved in various biological processes, such as vascular contractility, fibrosis, inflammation, oxidative stress, and apoptosis (Chen et al. 2013a; Chun et al. 2014).

Anti-obesity activities

S. chinensis fruit extract has been evaluated for inhibition effects on adipocyte differentiation in 3T3-L1 cells and anti-obesity properties in induced obese rats. S. chinensis fruit extracts inhibited preadipocyte differentiation and adipogenesis in cultured cells, leading to decreased body weight and fat tissue mass in high-fat diet obese rats (Park et al. 2012b).

Antiviral activity

The latest research has dealt with antiviral activity of dibenzocyclooctadiene lignans. Assays have shown that schisandrin B and deoxyschisandrin selectively inhibited the HIV-1 reverse transcriptase-associated DNA polymerase activity. Schisandrin B was able to impair the early phases of HIV-1 replication in cell-based assays. In addition, schisandrin B was also able to impair HIV-1 reverse transcriptase drug resistant mutants and the early phases of viral replication. Structure activity relationship revealed the importance of cyclooctadiene ring substituents for efficacy (Xu et al. 2015).

Schisandra lignans are also active against plant viruses. It has been demonstrated that the natural product—schisanthenol and its synthetic derivatives, were active against tobacco mosaic virus (Wang et al. 2015).