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According to modern herbology, BCT can be prescribed to treat phlegm discharge caused by upper respiratory infection or pneumonia and to ease chronic gastritis or morning sickness⁷⁾. These effects are accordant with the herbal characteristics of BCT, in that BCT has a sweet, yet chilling characteristic and its therapeutic effects converge mainly on the lung and stomach. However, limited studies are available that support the regulatory role of BCT in inflammatory diseases.

A recent study showed that BCT can be used to treat chronic obstructive pulmonary disease (COPD), a chronic inflammatory lung disease. In a cigarette-smoke-induced COPD mouse model, BCT reduced the expression of the prototypic pro-inflammatory cytokines, including IL-1β, IL-6, and TNF-α, and the infiltration of inflammatory cells, such as macrophages and neutrophils, in mouse lungs⁸⁾, suggesting that BCT has an anti-inflammatory function. Consistent with this result, p-coumaric acid, a primary chemical found in BCT, plays a role in suppressing inflammation in a similar mouse model⁹⁾. BCT was also reported to reduce the inflammatory symptoms associated with rheumatoid arthritis (RA)¹⁰⁾, the patients of which suffer from the degradation of proteins constituting cartilage and bone by various matrix metalloproteases (MMPs)¹¹⁾. MMP-3 is one of the metalloproteases involved in RA¹²⁾, whose production can be suppressed by BCT¹³⁾. Similarly, Bambusae caulis in Liquamen (BCL), a liquid extract of bamboo stems, suppressed inflammation in a 2,4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis (AD) mouse model¹⁴⁾. In the study, BCL was shown to decrease inflammatory cell infiltration into a skin lesion and the production of TNF-α and IFN-γ that exacerbate AD. It was reported that BCT can relieve hypertension and cardiovascular disease³⁾. Given that inflammation is one of the underlying causes of hypertension and cardiovascular diseases¹⁵⁾, the relieving effect of BCT could be due to inflammation suppressed by BCT. Together, these results suggest that the bamboo stem has anti-inflammatory activity, ameliorating various inflammatory diseases. As yet, however, no clinical studies with patients of COPD, RA, or AD are reported to consolidate these results.

Although the results indicate that BCT has an anti-inflammatory function, it is less understood how BCT suppresses inflammation. One of the possible mechanisms for BCT to suppress inflammation is via suppressing NF-κB activity. In COPD mice, BCT decreased the production of IL-1β, IL-6, and TNF-α⁸⁾. Since the expression of these cytokines is largely governed by NF-κB^16,17), it was examined whether BCT inhibits NF-κB activity. Indeed, the study revealed that BCT suppresses NF-κB activity⁸⁾, for which p-coumaric acid, a major chemical found in BCT, plays a key role⁹⁾. Concordant with these findings, we also found that BCT suppressed NF-κB activity. In our experiment, RAW 264.7 cells were treated with two different amounts of BCT (10 ng/ml or 50 ng/ml) for 16 hours and then with TLR-4 specific LPS to activate NF-κB in a TLR4-specific manner. We found that BCT suppressed the nuclear localization of NF-κB, suggesting BCT suppressing NF-κB. In similar experiments, where RAW 264.7 cells were treated with BCT and then with LPS (100 ng/ml) for 4 hours to induce NF-κB-dependent genes, BCT suppressed the TNF-α and IL-1β mRNA expression (data unpublished). Together, these results suggest that one of the anti-inflammatory pathways is via suppressing NF-κB activity.

The second possible mechanism is via activating the nuclear erythroid-2-related factor 2 (Nrf2). BCT was reported to increase heme oxygenase-1 (HO-1) expression by activating Nrf2 in RAW 264.7 cells¹⁸⁾. BCT also activates Nrf2 in microglial BV2 and hippocampal HT22 cells, protecting these cells from LPS-induced neuro-inflammation and glutamate-induced cytotoxicity, respectively¹⁹⁾. As a transcription factor, Nrf2 regulates the expression of cytoprotective and detoxifying genes, including glutamate- cysteine ligase catalytic subunit (GCLC), NAD(P)H:quinine oxidoreductase-1 (NQO1), and HO-1²⁰⁾. Along with the anti-oxidative , Nrf2 suppresses inflammation because the absence of Nrf2 exacerbates inflammatory diseases, including acute lung injury (ALI)²¹⁾, chronic obstructive pulmonary disease (COPD)²²⁾, asthma²³⁾, and sepsis²⁴⁾. Given the anti-inflammatory role of Nrf2, activating Nrf2 is one of the pathways that BCT suppresses inflammation. In support of this, our studies revealed that BCT activates Nrf2 (data unpublished). If RAW 264.7 cells were treated with two different amounts of BCT (10 ng/ml or 50 ng/ml) for 16 hours, Nrf2 is translocated to the nucleus, indicative of activated Nrf2. In similar experiments, BCT induced the expression of HO-1, GCLC, and NQO-1, whose expression is regulated by Nrf2. Along with others, these results further support that BCT suppresses inflammation via activating Nrf2.

The third possible pathway is via inducing A20 or tumor necrosis factor-induced protein 3 (TNFAIP3), an anti-inflammatory adaptor molecule that suppresses NF-κB activity¹⁷⁾. An inflammatory environment triggers the expression of A20, which blocks the IL-1β receptor- or TLR4-mediated signaling, decreasing the expression of pro-inflammatory cytokines and consequently inhibiting inflammation²⁵⁾. Given the anti-inflammatory role of A20, we examined whether BCT induces A20 expression. RAW 264.7 cells were treated with increasing amounts of BCT for 16 h. Western blot analysis of cytosolic proteins showed that BCT induced the expression of A20 (data unpublished). While further studies are necessary to consolidate BCT activating A20, these results suggest that BCT can suppress inflammation in at least three different ways: suppressing NF-κB, activating Nrf2, and inducing A20.

Given that BCT has anti-inflammatory activity, we looked up the decoctions that have BCT as the main herb or 君藥, and found that Chikujountanto (TJ-091) in Japanese Kampo medicine and Jukyeoondam-Tang (竹茹溫膽湯, JOT) in China^26,27) have been prescribed to relieve fever, coughing, and phlegm production caused by respiratory infection²⁸⁾. In Japan, TJ-091, equivalent to JOT, has been used to treat Covid-19 patients²⁹⁾. Collectively, the indications (適應症) or symptoms treated by these BCT-containing decoctions are related to the anti-inflammatory function of BCT. However, in Korea, similar decoctions containing BCT as the major herb seem to have different medical indications.

Korean Ministry of Food and Drug Safety (KFDA) enlists 11 different decoctions that contain BCT as a major herb; they can be categorized into 3 groups: Gwibi-tang / Hapyeoldahanso-tang (歸脾湯合熱多寒少湯), Gamiondam-tang (加味溫膽湯, GOT), and Ondam-tang (溫膽湯) (Table 1). Although the compositions are varied, all of them are prescribed to relieve headaches, insomnia, nervousness, or abnormal responsiveness to stimulation (erethism). Of note, the composition of GOT is almost identical to JOT, except Coptis chinesis (黃連). GOT was approved for relieving neurologic symptoms in Korea, while JOT was for inflammatory pulmonary symptoms in Japan and China. In composition, GOT contains Z. jujuba (Fructus), instead of C. chinesis. Conversely, JOT does C. chinesis, in the place of Z. jujuba (Fructus). It is noteworthy that both Z. jujuba (Fructus)³⁰⁾ and C. chinesis³¹⁾ have anti-inflammatory activity. Thus, C. chinesis is interchangeable with Z. jujuba (Fructus). If taken as the case, one can say that GOT is almost identical to JOT in terms of therapeutic effect. Then, GOT may apply to treating inflammatory diseases.

Nevertheless, it remains unclear why the two decoctions, Chikujountanto or JOT and GOT are being used to treat different indications, depending on countries. These divergent applications of a BCT-containing decoction for different medical indications could be related to how Korean medicine interprets the role of BCT when formulating decoctions. Alternatively, neuronal disorders treated by GOT may be associated with neuronal inflammation, and thus both GOT and JOT target a similar, if not the same, inflammatory mechanism. However, this possibility needs to be verified by experiments. In Korea, BCT-containing decoctions seem not popular in the clinic, although precise statistical data are not available. Given the anti-inflammatory activity of BCT as a major herb and that JOT and GOT are almost identical in their compositions, it would be reasonable that the medical indications treated by GOT and other BCT-containing decoctions in Korea can be extended to treating inflammatory symptoms.